M.M. Dominello

Radiation-Induced Esophagitis is Mitigated by Soy Isoflavones

Introduction Lung cancer patients receiving radiotherapy present with acute esophagitis and chronic fibrosis, as a result of radiation injury to esophageal tissues. We have shown that soy isoflavones alleviate pneumonitis and fibrosis caused by radiation toxicity to normal lung. The effect of soy isoflavones on esophagitis histopathological changes induced by radiation was investigated. Methods C57BL/6 mice were treated with 10 Gy or 25 Gy single thoracic irradiation and soy isoflavones for up to 16 weeks. Damage to esophageal tissues was assessed by hematoxylin–eosin, Masson’s Trichrome and Ki-67 staining at 1, 4, 10, and 16 weeks after radiation. The effects on smooth muscle cells and leukocyte infiltration were determined by immunohistochemistry using anti-αSMA and anti-CD45, respectively. Results Radiation caused thickening of esophageal tissue layers that was significantly reduced by soy isoflavones. Major radiation alterations included hypertrophy of basal cells in mucosal epithelium and damage to smooth muscle cells in muscularis mucosae as well as disruption of collagen fibers in lamina propria connective tissue with leukocyte infiltration. These effects were observed as early as 1 week after radiation and were more pronounced with a higher dose of 25 Gy. Soy isoflavones limited the extent of tissue damage induced by radiation both at 10 and 25 Gy. Conclusion Soy isoflavones have a radioprotective effect on the esophagus, mitigating the early and late effects of radiation injury in several esophagus tissue layers. Soy could be administered with radiotherapy to decrease the incidence and severity of esophagitis in lung cancer patients receiving thoracic radiation therapy.

Target Volume Heterogeneity Index, a Potentially Valuable Metric in IMRT Prostate Cancer Treatment Planning

Abstract Purpose/Objectives: Heterogeneity index (HI) has been described in the literature as a tool for evaluating dose gradients within a planning target volume (PTV). HI may be expressed as D1/D95 where D1 and D95 equal the dose encompassing 1% and 95% of the target volume. The purpose of this study is to evaluate the effect of target volume dose heterogeneity on dose received by local organs at risk in the treatment of low and intermediate risk prostate cancer. Materials/Methods: Treatment plans were reviewed for 157 patients with low or intermediate risk prostate cancer treated with dose-escalated radiation therapy between 6/2007 and 2/2012. Patients treated in the post-operative setting or receiving pelvic nodal irradiation were excluded. Patients were treated with either standard intensity modulation (IMRT) using 7 or 8 fields or 2-arc volumetric modulated arc therapy (VMAT). All patients had daily image-guidance. PTV HI (D1/D95) and dose-volume histogram (DVH) data at 8 dose levels for rectum and bladder were recorded. Patients were categorized into two groups (low HI or high HI) with respect to median index score. A two-tailed t-test was used to test for differences in dose received by rectum and bladder for the two groups. Results: For the 157 plans evaluated, mean PTV volume was 164cc and mean prescription dose was 7833cGy. Median HI was 1.04 (range 1.0-1.08). Low HI (≤1.04) was found to correlate with significantly lower rectal V50 (p=0.02), V55 (p=0.01), V60 (p=0.01), V65 (p=0.01), and V70 (p=0.01). There was no significant correlation with dose received by bladder at any dose level. HI was similar for patients treated with standard IMRT and VMAT (p=0.85). Conclusions: Target volume HI ≤1.04 is associated with more favorable rectal doses at clinically relevant dose-levels. We believe HI may serve as a valuable metric in prostate cancer treatment planning. Further work is needed to correlate these dosimetric findings with clinical outcomes.

Patterns and predictors of failure following tri-modality therapy for locally advanced esophageal cancer.

Abstract Background. Although tri-modality therapy is an acceptable standard of care in patients with locally advanced esophageal cancer, data regarding patterns of failure is lacking. We report bi-institutional patterns of failure experience treating patients using tri-modality therapy. Materials and methods. We retrospectively reviewed patients who underwent chemoradiation followed by esophagectomy between 2006 and 2011 at two NCI-designated cancer centers. First failure sites were categorized as local, regional nodal, or distant. Statistical analysis was performed using Fisher’s exact test, non-parametric Wilcoxon rank-sum test, and multiple logistic regression. Kaplan-Meier curves were generated for relapse-free survival (RFS) and overall survival. Results. A total of 132 patients met the inclusion criteria with a median age of 62 (range 36–80) and median follow-up of 28 months (range 4–128). There were a total of six (4.5%) local, 13 (10%) regional nodal, and 32 (23.5%) distant failures. Local failure was correlated with fewer lymph nodes (LN) assessed (p = 0.01) and close/positive margins (p < 0.01). Regional nodal failure was correlated with fewer LN assessed (p < 0.01) and larger pretreatment tumor size (p = 0.04). Patients with ≤13 LN evaluated had an inferior locoregional RFS versus patients with >13 LN evaluated (p = 0.003). Distant recurrence was correlated with higher pathologic nodal stage (p < 0.001), ulceration (p = 0.017), perineural invasion (p = 0.029), residual disease (p = 0.004), and higher post-treatment PET SUV max (p = 0.049). Patients with a pathologic complete response (OR 0.19, 95% CI 0.05–0.68) were less likely to experience distant recurrence. Conclusion. Tumor and treatment factors may predict for failure in patients undergoing tri-modality therapy for locally advanced esophageal cancer. Further data is needed to identify patterns of failure in these patients.

Limitations of the bowel bag contouring technique in the definitive treatment of cervical cancer

PURPOSE Incidence of acute grade 3 and 4 small bowel toxicity in the definitive treatment of cervical cancer is approximately 15%. Given uncertainties in position of the bowel at time of treatment, techniques including the contouring of a bowel bag have been suggested. The purpose of this study is to describe interfraction variability in bowel location for the female pelvis with intact reproductive organs and to characterize the ability of the bowel bag technique, as described in the Radiation Therapy Oncology Group pelvic normal tissue contouring guidelines, to account for organ motion in this specific clinical setting. METHODS AND MATERIALS Bowel position was assessed for 45 computed tomographic scans used in treatment planning for 9 consecutive cervical cancer patients. After a single operator contoured bowel loops, most superior, anterior, posterior, and inferior positions of bowel were recorded. Mixed effects models were used to assess significance of interfraction variability. Frequency of bowel loop migration outside of the bowel bag was then considered for each patient given all potential bowel bag volumes. Standardized scoring was used to determine additional margins that would be required to account for 95%, 90%, and 85% of significant bowel motion. RESULTS Interfraction variability in the inferior-most bowel position was significant (P = .002). Median maximum variation in the inferior bowel position was 2.1 cm (range, 0.9 cm-4.8 cm). When applying the bowel bag technique, 100% of bowel motion was accounted for as the bowel translated laterally, anteriorly, posteriorly, and superiorly, though accounted for just 70.3% of motion in the inferior direction. A 4-cm inferior margin was required to account for 90% of motion in the inferior direction. CONCLUSIONS In the intact female pelvis, the bowel bag technique is successful in accounting for most interfraction variability in bowel position but underestimates inferior motion. Until an improved approach to predicting small bowel motion can be routinely implemented, a focus on decreasing dose to potential bowel space should be emphasized.

Radiotherapy and radioembolization for liver metastases

Liver metastases are a common source of cancer-related morbidity. While systemic palliative chemotherapy is an option for patients with significant metastatic disease burden, radiotherapy (RT) is a safe, well-tolerated local treatment that can offer durable tumor control and relief of symptoms. Innovations in RT delivery now allow for treatment of liver metastases in one to five sessions with high local control rates. There is a growing body of Phase I-II data supporting the use of such RT techniques, including stereotactic body radiotherapy (SBRT) and radioembolization for the treatment of liver metastases. While there are a variety of local therapies available to patients with liver metastases, RT should be strongly considered in patients with liver metastasis related pain or oligometastatic disease not amenable to surgery. We recommend a multidisciplinary approach when weighing the risks and benefits of the available local treatment modalities for each patient.

Pretreatment computed tomographic gross tumor volume as predictor of persistence of tracheostomy and percutaneous endoscopic gastrostomy tube in patients undergoing larynx preservation

Although larynx preservation affords patients improvements in laryngectomy‐free survival, little has been reported regarding the functional outcomes after larynx preservation. The purpose of this study was to report the predictive value of pretreatment CT‐gross tumor volume (GTV) for persistence of tracheostomy and percutaneous endoscopic gastrostomy (PEG) tube in larynx preservation patients.

Outcomes of Elderly Patients Who Receive Combined Modality Therapy for Locally Advanced Non–Small-Cell Lung Cancer

Background: The objective of this study was to review our institutions experience among patients with locally advanced non–small‐cell lung cancer (LA‐NSCLC) treated with chemotherapy and radiation and to determine the prognostic significance of age. Patients and Methods: Patients were included if they underwent sequential or concurrent chemoradiotherapy from 2006 to 2014 for LA‐NSCLC. Patients were stratified according to age ≤70 and >70 years. Kaplan–Meier and Cox regression methods were performed to evaluate overall survival (OS) and progression‐free survival (PFS). Results: One hundred twenty‐three patients were identified. Ninety‐eight patients were 70 years of age or younger and 25 patients were older than 70 years of age. The median radiotherapy dose was 6660 cGy (range, 3780–7600 cGy). A greater percentage of elderly patients were men, 72% (18 patients) versus 39% (38 patients) (P = .006) and received carboplatin/paclitaxel‐based chemotherapy, 60% (15 patients) versus 21% (20 patients) (P < .001). Median follow‐up for OS was 25.9 (95% confidence interval [CI], 21.3–33.9) months. There was no difference in the PFS of older patients versus younger patients (hazard ratio [HR], 1.15; P = .64), adjusted for significant covariates. The 1‐year PFS rate for patients 70 years of age or younger was 51% (95% CI, 42%‐63%) versus 45% (95% CI, 28%‐71%) in patients older than 70 years. After adjusting for significant covariates, there was no difference in the OS of older patients compared with younger patients (HR, 1.18; P = .65). The 1‐year OS rate for patients 70 years of age or younger was 77% (95% CI, 68%‐86%) versus 56% (95% CI, 39%‐81%) in patients younger than 70 years. Conclusion: Chemoradiotherapy is an effective treatment in elderly patients with LA‐NSCLC, with outcomes similar to that in younger patients. Appropriately selected elderly patients should be considered for chemoradiation. Micro‐Abstract: Our objective was to determine the significance of age in patients treated with sequential or concurrent chemoradiotherapy for locally advanced non–small‐cell lung cancer (LA‐NSCLC). Ninety‐eight patients were 70 years of age or younger and 25 were older than 70 years. In multivariable analysis, there was no difference in the progression‐free survival (hazard ratio [HR], 1.15; P = .64) or overall survival (HR, 1.18; P = .65) of older versus younger patients. Chemoradiotherapy is an effective treatment in elderly patients with LA‐NSCLC, with outcomes similar to that in younger patients.

Intratumoral lymphatic vessel density as a predictor of progression-free and overall survival in locally advanced laryngeal/hypopharyngeal cancer

Lymphatic vessel density (LVD) has been shown to be an important predictor of survival in head and neck cancers. We report the predictive value of LVD for progression‐free survival (PFS) and overall survival (OS) in laryngeal/hypopharyngeal cancer.

Glioblastoma metastatic to the ovary, a very different Krukenberg tumor?

We report the case of a 24-year-old African-American female with metastatic World Health Organization grade IV glioblastoma (GBM). Following treatment for her primary right frontal brain tumor, the patient presented with metastasis to the lung, liver, and ovary, demonstrating the first reported case of GBM metastasis to the ovary. The patient presented with bifrontal headaches, drowsiness, and dizziness in September 2009.Magnetic resonance imaging scans demonstrated a 4.6 cm contrast enhancing right frontal mass with vasogenic edema. A right frontal craniotomy with stereotactic, volumetric gross total resection was performed. Upon pathologic examination, the specimen demonstrated anaplasia, necrosis, and high proliferative index (Ki-67 N50%), rendering it consistent with GBM diagnosis. Postoperatively, the patient experienced mild left-sided weakness. The patient received radiation therapy (RT) targeting the resection cavity to 50.4 Gy, in 1.8 Gy/fraction, with a 10.8 Gy boost completed January 26, 2010 (cumulative dose, 61.2 Gy), with concurrent temozolomide (75 mg/m2

Helical Therapy is Safe for Lung Stereotactic Body Radiation Therapy Despite Limitations in Achieving Sharp Dose Gradients

Purpose: We observed that many of our helical therapy lung stereotactic body radiation therapy plans did not meet the Radiation Therapy Oncology Group (RTOG) recommended R50% (volume of 50% of the prescription dose/planning target volume), which characterizes the steepness of dose fall off. We hypothesized that despite not meeting R50%, helical therapy lung stereotactic body radiation therapy plans would confer similar local control and minimal side effects as previously reported using nonhelical treatment platforms. Materials and Methods: We report a retrospective review of all consecutive patients treated off-protocol with stereotactic body radiation therapy for peripheral lung lesions from 2008 to 2013 utilizing helical therapy. Seventy-four patients (81 lesions and 79 plans) were treated with doses ranging from 48 to 60 Gy in 3 to 5 fractions prescribed to the edge of the planning target volume. Results: Forty-eight (61%) plans had major deviation from R50%. Only 1 (<1%) plan had a major deviation from the R100%. All plans had > 95% planning target volume coverage by prescription dose, 7(8.6%) plans with 121% to 133% maximum dose, and lung V20 Gy <10% in 70 (89%) plans. With a median follow-up of 4.7 years (95% confidence interval: 4.1-5.3), local control for all patients at 1, 2, and 5 years was 94.6%, 83.4%, and 74%, respectively. For patients with primary stage I-II lung cancer (n = 46), the 1, 2, and 5-year local control: 97.2%, 94.2%, and 86.9%; RC: 97.6%, 82.5%, and 69.5%; and DM: 3%, 16%, and 33.4%, respectively. Patients treated for lung metastases (n = 26) had worse local control at 1, 2, and 5 years: 94.4%, 69.3%, and 55.5%, respectively. Side effects were rare with 2 (3%) patients reporting chest wall pain and 6 (8%) patients experiencing radiation pneumonitis, including 1 patient who had grade 5 radiation pneumonitis. Conclusions: Helical therapy delivers a safe and effective lung stereotactic body radiation therapy plan, despite not being able to meet RTOG’s recommended R50 conformality constraint.