Michael C. Stauder

Stereotactic Body Radiation Therapy in Spinal Metastases

PURPOSE Based on reports of safety and efficacy, stereotactic body radiotherapy (SBRT) for treatment of malignant spinal tumors was initiated at our institution. We report prospective results of this population at Mayo Clinic. MATERIALS AND METHODS Between April 2008 and December 2010, 85 lesions in 66 patients were treated with SBRT for spinal metastases. Twenty-two lesions (25.8%) were treated for recurrence after prior radiotherapy (RT). The mean age of patients was 56.8 ± 13.4 years. Patients were treated to a median dose of 24 Gy (range, 10-40 Gy) in a median of three fractions (range, 1-5). Radiation was delivered with intensity-modulated radiotherapy (IMRT) and prescribed to cover 80% of the planning target volume (PTV) with organs at risk such as the spinal cord taking priority over PTV coverage. RESULTS Tumor sites included 48, 22, 12, and 3 in the thoracic, lumbar, cervical, and sacral spine, respectively. The mean actuarial survival at 12 months was 52.2%. A total of 7 patients had both local and marginal failure, 1 patient experienced marginal but not local failure, and 1 patient had local failure only. Actuarial local control at 1 year was 83.3% and 91.2% in patients with and without prior RT. The median dose delivered to patients who experienced local/marginal failure was 24 Gy (range, 18-30 Gy) in a median of three fractions (range, 1-5). No cases of Grade 4 toxicity were reported. In 1 of 2 patients experiencing Grade 3 toxicity, SBRT was given after previous radiation. CONCLUSION The results indicate SBRT to be an effective measure to achieve local control in spinal metastases. Toxicity of treatment was rare, including those previously irradiated. Our results appear comparable to previous reports analyzing spine SBRT. Further research is needed to determine optimum dose and fractionation to further improve local control and prevent toxicity.

Early pulmonary toxicity following lung stereotactic body radiation therapy delivered in consecutive daily fractions

BACKGROUND AND PURPOSE Identify the incidence of early pulmonary toxicity in a cohort of patients treated with lung stereotactic body radiation therapy (SBRT) on consecutive treatment days. MATERIAL AND METHODS A total of 88 lesions in 84 patients were treated with SBRT in consecutive daily fractions (Fx) for medically inoperable non-small cell lung cancer or metastasis. The incidence of pneumonitis was evaluated and graded according to the NCI CTCAE v3.0. RESULTS With a median follow-up of 15.8 months (range 2.5-28.6), the median age at SBRT was 71.8 years (range 23.8-87.8). 47 lesions were centrally located and 41 were peripheral. Most central lesions were treated with 48Gy in 4 Fx, and most peripheral lesions with 54Gy in 3 Fx. The incidence of grade ≥ 2 pneumonitis was 12.5% in all patients treated, and 14.3% among the subset of patients treated with 54Gy in 3 Fx. A total of two grade 3 toxicities were seen as one grade 5 toxicity in a patient treated for recurrence after pneumonectomy. CONCLUSIONS Treating both central and peripheral lung lesions with SBRT in consecutive daily fractions in this cohort was well tolerated and did not cause excessive early pulmonary toxicity.

Acute and Short-term Toxic Effects of Conventionally Fractionated vs Hypofractionated Whole-Breast Irradiation: A Randomized Clinical Trial

IMPORTANCE The most appropriate dose fractionation for whole-breast irradiation (WBI) remains uncertain. OBJECTIVE To assess acute and 6-month toxic effects and quality of life (QOL) with conventionally fractionated WBI (CF-WBI) vs hypofractionated WBI (HF-WBI). DESIGN, SETTING, AND PARTICIPANTS Unblinded randomized trial of CF-WBI (n = 149; 50.00 Gy/25 fractions + boost [10.00-14.00 Gy/5-7 fractions]) vs HF-WBI (n = 138; 42.56 Gy/16 fractions + boost [10.00-12.50 Gy/4-5 fractions]) following breast-conserving surgery administered in community-based and academic cancer centers to 287 women 40 years or older with stage 0 to II breast cancer for whom WBI without addition of a third field was recommended; 76% of study participants (n = 217) were overweight or obese. Patients were enrolled from February 2011 through February 2014 and observed for a minimum of 6 months. INTERVENTIONS Administration of CF-WBI or HF-WBI. MAIN OUTCOMES AND MEASURES Physician-reported acute and 6-month toxic effects using National Cancer Institute Common Toxicity Criteria, and patient-reported QOL using the Functional Assessment of Cancer Therapy for Patients with Breast Cancer (FACT-B). All analyses were intention to treat, with outcomes compared using the χ2 test, Cochran-Armitage test, and ordinal logistic regression. RESULTS Of 287 participants, 149 were randomized to CF-WBI and 138 to HF-WBI. Treatment arms were well matched for baseline characteristics, including FACT-B total score (HF-WBI, 120.1 vs CF-WBI, 118.8; P = .46) and individual QOL items such as somewhat or more lack of energy (HF-WBI, 38% vs CF-WBI, 39%; P = .86) and somewhat or more trouble meeting family needs (HF-WBI, 10% vs CF-WBI, 14%; P = .54). Maximum physician-reported acute dermatitis (36% vs 69%; P < .001), pruritus (54% vs 81%; P < .001), breast pain (55% vs 74%; P = .001), hyperpigmentation (9% vs 20%; P = .002), and fatigue (9% vs 17%; P = .02) during irradiation were lower in patients randomized to HF-WBI. The rate of overall grade 2 or higher acute toxic effects was less with HF-WBI than with CF-WBI (47% vs 78%; P < .001). Six months after irradiation, physicians reported less fatigue in patients randomized to HF-WBI (0% vs 6%; P = .01), and patients randomized to HF-WBI reported less lack of energy (23% vs 39%; P < .001) and less trouble meeting family needs (3% vs 9%; P = .01). Multivariable regression confirmed the superiority of HF-WBI in terms of patient-reported lack of energy (odds ratio [OR], 0.39; 95% CI, 0.24-0.63) and trouble meeting family needs (OR, 0.34; 95% CI, 0.16-0.75). CONCLUSIONS AND RELEVANCE Treatment with HF-WBI appears to yield lower rates of acute toxic effects than CF-WBI as well as less fatigue and less trouble meeting family needs 6 months after completing radiation therapy. These findings should be communicated to patients as part of shared decision making. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01266642.

Immunogenicity of the Hu14.18-IL2 Immunocytokine Molecule in Adults With Melanoma and Children With Neuroblastoma

Purpose: Immunocytokine (IC) hu14.18-IL2 is a fusion protein of humanized antidisialoganglioside (GD2) antibody (hu14.18) and interleukin (IL)-2. Sixty-one melanoma and neuroblastoma patients received IC in phase I/Ib studies. Patient sera were examined in ELISA to determine if an anti-IC antibody response occurred during treatment. Experimental Design: Serum was assayed for anti-idiotypic antibody (anti-id Ab) based on ability to bridge biotinylated hu14.18 to plate-bound hu14.18 and ability to inhibit binding of hu14.18 to GD2 antigen and/or murine anti-idiotypic antibody. ELISA was also used to detect antibodies to the Fc-IL2 end of hu14.18-IL2. Results: Thirty-two patients (52%) developed an anti-idiotypic antibody response (absorbance, >0.7) in the bridge ELISA. Twelve patients (20%) had an intermediate response, whereas 17 patients (28%) were negative (adsorbance, <0.3). The development of antibody to hu14.18-IL2 detected in the bridge ELISA was not related to the dose of hu14.18-IL2. Twenty of 33 adult patients (61%) demonstrated an anti-idiotypic antibody response based on binding inhibition ELISA. The anti-idiotypic response was inversely correlated (P < 0.002) with IC measured during the second course of treatment, indicating that development of anti-idiotypic antibodies interfered with detection of circulating hu14.18-IL2. All patients developed some inhibitory activity in the binding inhibition assay designed to detect antibodies to the Fc-IL2 region of the IC. There was a positive correlation between the peak serum level of IC in course 1 and the anti–Fc-IL2 response. Conclusions: Patients treated with hu14.18-IL2 developed anti-idiotypic antibodies and anti Fc-IL2 antibodies. No association was seen between development of anti-IC antibodies and clinical toxicity. (Clin Cancer Res 2009;15(18):5923–30)

Longitudinal analysis of patient-reported outcomes and cosmesis in a randomized trial of conventionally fractionated versus hypofractionated whole-breast irradiation.

The authors compared longitudinal patient‐reported outcomes and physician‐rated cosmesis with conventionally fractionated whole‐breast irradiation (CF‐WBI) versus hypofractionated whole‐breast irradiation (HF‐WBI) within the context of a randomized trial.

Late tumor pseudoprogression followed by complete remission after lung stereotactic ablative radiotherapy

Lung stereotactic ablative radiotherapy (SABR) has recently become more common in the management of patients with early-stage non-small cell lung cancer (NSCLC) and metastatic lung lesions who are not surgical candidates. By design, SABR is applied to small treatment volumes, using fewer but significantly higher dose fractions, and steep dose gradients. This treatment theoretically maximizes tumor cell death and decreases the risk of damage to the surrounding normal tissues. Local control rates for SABR in early stage lung cancer remain high. Since the numbers of primary tumor recurrences is small, some debate exists as to the appropriate definition of treatment failure. Controversies remain regarding the most appropriate interpretation of imaging tests obtained to evaluate treatment outcomes after lung SABR. Most definitions of progression include an increasing diameter of target lesion which can be problematic given the known mass-like consolidation seen on CT imaging after ablative therapy. Here, we present a case report illustrative of the pitfalls of relying solely on anatomic imaging to determine SABR treatment failure.

Prognosis for patients with metastatic breast cancer who achieve a no-evidence-of-disease status after systemic or local therapy.

This study sought to determine outcomes for patients with metastatic breast cancer (MBC) with no evidence of disease (NED) after treatment and to identify factors predictive of outcomes once the status of NED was attained.

Once-daily radiation therapy for inflammatory breast cancer.

PURPOSE Inflammatory breast cancer (IBC) is a rare and aggressive breast cancer variant treated with multimodality therapy. A variety of approaches intended to escalate the intensity and efficacy of radiation therapy have been reported, including twice-daily radiation therapy, dose escalation, and aggressive use of bolus. Herein, we examine our outcomes for patients treated with once-daily radiation therapy with aggressive bolus utilization, focusing on treatment technique. METHODS AND MATERIALS A retrospective review of patients with nonmetastatic IBC treated from January 1, 2000, through December 31, 2010, was performed. Locoregional control (LRC), disease-free survival (DFS), overall survival (OS) and predictors thereof were assessed. RESULTS Fifty-two women with IBC were identified, 49 (94%) of whom were treated with neoadjuvant chemotherapy. All underwent mastectomy followed by adjuvant radiation therapy. Radiation was delivered in once-daily fractions of 1.8 to 2.25 Gy (median, 2 Gy). Patients were typically treated with daily 1-cm bolus throughout treatment, and 33 (63%) received a subsequent boost to the mastectomy scar. Five-year Kaplan Meier survival estimates for LRC, DFS, and OS were 81%, 56%, and 64%, respectively. Locoregional recurrence was associated with poorer OS (P<.001; hazard ratio [HR], 4.1). Extracapsular extension was associated with worse LRC (P=.02), DFS (P=.007), and OS (P=.002). Age greater than 50 years was associated with better DFS (P=.03). Pathologic complete response was associated with a trend toward improved LRC (P=.06). CONCLUSIONS Once-daily radiation therapy with aggressive use of bolus for IBC results in outcomes consistent with previous reports using various intensified radiation therapy regimens. LRC remains a challenge despite modern systemic therapy. Extracapsular extension, age ≤50 years, and lack of complete response to chemotherapy appear to be associated with worse outcomes. Novel strategies are needed in IBC, particularly among these subsets of patients.

Excellent local control and survival after intraoperative and external beam radiotherapy for pediatric solid tumors: Long-term follow-up of the mayo clinic experience

Use of external beam radiotherapy (EBRT) for pediatric solid malignancies is generally limited by the tolerance of normal tissue in developing organs. Intraoperative electron radiotherapy (IOERT) allows a more focal delivery of radiation dose because vital organs can be displaced and avoided during treatment. From February 1983 to July 2003, 20 children underwent IOERT for treatment of locally advanced or recurrent malignancies of the extremity or abdominopelvic area. All patients underwent EBRT and received IOERT doses of 7.5 to 25 Gy with 6-MeV to 15-MeV electrons. At a median follow-up of 11.6 years (range, 2.1 to 25.5 y), 13 patients (65%) were alive and without evidence of disease. Patients who underwent gross total resection had better local control (88% vs. 67%) and survival (71% vs. 33%) than patients for whom the resection was not achieved. Among 7 patients, 11 grade 3 toxicity events were reported. No grade >3 toxicities or second malignancies were observed during follow-up. Use of IOERT in combination with surgery and EBRT in management of pediatric solid malignancies provides excellent local control with reasonable toxicity. IOERT should be considered as an integral part of a multimodality regimen for pediatric solid malignancies, especially for patients with abdominopelvic malignancies.

Long-term treatment outcomes for locally advanced esophageal cancer: A single-institution experience

Objectives:To determine long-term outcomes in patients with locally advanced esophageal carcinoma treated with trimodality therapy (chemoradiotherapy [CRT] and surgery, TMT) or definitive CRT. Methods:We retrospectively identified patients with advanced esophageal carcinoma treated with curative intent at our institution between 1998 and 2004. Identified patients were separated into 3 groups: patients who received TMT, patients who received CRT, and patients who began treatment with trimodality intent but did not undergo surgery (PTMT). Local control, overall survival (OS), and distant metastasis-free survival were compared using Kaplan-Meier statistics. Results:Among the 265 patients included, median follow-up was 6.4 years for surviving patients and 1.7 years for all patients. Type of esophageal cancer was adenocarcinoma in 213 patients (80%) and squamous cell carcinoma in 46 patients (17%). Treatment groups comprised 169 patients (64%) completing TMT, 46 patients medically unable to undergo surgery after neoadjuvant therapy (PTMT), and 50 (19%) who underwent CRT. Median OS was 20.5 months; actuarial 5- and 10-year OS were 27% and 12%, respectively. The TMT group had the highest 5- and 10-year OS (32% and 19%, respectively). Local control rates at 2, 5, and 10 years for all patients were 80%, 70%, and 69%, respectively. By treatment modality, 5-year local control was best (82%) for TMT, compared with 60% for CRT and 40% for PTMT groups (P<0.001). Conclusions:Patients who completed TMT had the best local control and long-term OS. In the context of TMT, surgery seemed more beneficial in patients with esophageal adenocarcinoma versus squamous cell carcinoma.