P.A. Paximadis

Up-front neck dissection followed by concurrent chemoradiation in patients with regionally advanced head and neck cancer.

The appropriate management of the neck in patients with regionally advanced head and neck cancer remains controversial. The purpose of this study was to retrospectively analyze our institutional experience with up‐front neck dissection followed by definitive chemoradiotherapy.

Patterns of Failure in Patients With Primary Intracranial Germinoma Treated With Neoadjuvant Chemotherapy and Radiotherapy

External beam radiotherapy has proven effective in managing intracranial germinoma. However, concerns regarding long-term neurocognitive and endocrine sequelae led to the addition of chemotherapy, to reduce radiation target volumes. There is a paucity of data on patterns of failure in patients treated with differing radiation field sizes. We review our experience at a tertiary childrens hospital treating children with intracranial germinoma, using induction chemotherapy followed by radiation therapy to various treatment volumes (craniospinal irradiation, whole ventricular irradiation, whole brain radiation therapy, and focal radiotherapy). Ten patients with primary intracranial germinoma, treated from November 1995-March 2011, were included. The primary treatment involved platinum-based chemotherapy, followed by definitive radiotherapy. The median follow-up period was 4.3 years (range, 0.75-13.25 years). The 5-year overall survival for the entire group was estimated at 85.7%, and the 5-year disease-free survival was estimated at 75.0%. Two treatment failures occurred at 5 and 28 months, both in patients with single lesions in the pineal region treated with focal radiotherapy only. Based on the patterns of failure, our outcomes support the continued use of the whole ventricular field vs a focal field, even in patients with limited disease who demonstrate a complete response to neoadjuvant chemotherapy.

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.

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.

The interaction between androgen receptor and PDGF-D in the radiation response of prostate carcinoma.

To determine the functional relationship between androgen receptor (AR) and PDGF D as it relates to the radiation response of PTEN‐null prostate cancer (PCa) cells and the effect of enzalutamide on these interactions.

Dosimetric predictors for acute esophagitis during radiation therapy for lung cancer: Results of a large statewide observational study

PURPOSE The purpose of this study is to identify dosimetric variables that best predict for acute esophagitis in patients treated for locally advanced non-small cell lung cancer in a prospectively accrued statewide consortium. METHODS AND MATERIALS Patients receiving definitive radiation therapy for stage II-III non-small cell lung cancer within the Michigan Radiation Oncology Quality Consortium were included in the analysis. Dose-volume histogram data were analyzed to determine absolute volumes (cc) receiving doses from 10 to 60 Gy (V10, V20, V30, V40, V50, and V60), as well as maximum dose to 2 cc (D2cc), mean dose (MD), and generalized equivalent uniform dose (gEUD). Logistic regression models were used to characterize the risk of toxicity as a function of dose and other covariates. The ability of each variable to predict esophagitis, individually or in a multivariate model, was quantified by receiver operating characteristic analysis. RESULTS There were 533 patients who met study criteria and were included; 437 (81.9%) developed any grade of esophagitis. Significant variables on univariate analysis for grade ≥2 esophagitis were concurrent chemotherapy, V20, V30, V40, V50, V60, MD, D2cc, and gEUD. For grade ≥3 esophagitis, the predictive variables were: V30, V40, V50, V60, MD, D2cc, and gEUD. In multivariable modeling, gEUD was the most significant predictor of both grade ≥2 and grade ≥3 esophagitis. When gEUD was excluded from the model, D2cc was selected as the most predictive variable for grade ≥3 esophagitis. For an estimated risk of grade ≥3 esophagitis of 5%, the threshold values for gEUD and D2cc were 59.3 Gy and 68 Gy, respectively. CONCLUSIONS In this study, we report the novel finding that gEUD and D2cc, rather than MD, were the most predictive dose metrics for severe esophagitis. To limit the estimated risk of grade ≥3 esophagitis to <5%, thresholds of 59.3 Gy and 68 Gy were identified for gEUD and D2cc, respectively.

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.

Dosimetric evaluation of Point A and volume-based high-dose-rate plans: a single institution study on adaptive brachytherapy planning for cervical cancer

Purpose External beam radiation therapy (EBRT) and brachytherapy (BT) with concurrent cisplatin is the standard of care for locally advanced cervical cancer. The applicability of image-guided adaptive volume-based high-dose-rate (HDR) intracavitary brachytherapy planning is an active area of investigation. In this study, we examined whether volume-based HDR-BT (HDRVOL) plans leads to more conformal plans compared to Point A (HDRPointA)-based plans. Material and methods Two hundred and forty HDRPointA plans from 48 cervical cancer patients treated with chemoradiotherapy were retrospectively collected. Point A plans were renormalized with respect to the high-risk clinical target volume (HR-CTV) for the HDRVOL plans. The doses to organs at risk (OAR; rectum, sigmoid, and bladder), and HR-CTV and the conformal index were compared between HDRPointA and HDRVOL plans. Results HDRVOL plans resulted in a 6-12% reduction in the total dose (EBRT + HDR-BT) to 0.1 cc, 1.0 cc, and 2.0 cc of the OAR as well as an 8-37% reduction in the dose to 2 cc of OAR per HDR-BT fraction compared to HDRPointA plans. Differences in the conformal indexes between the two groups of plans showed an 18-31% relative increase per HDR-BT fraction for HDRVOL plans. The D90 of the HR-CTV was reduced by 11% by HDRVOL planning and had a median dose of 86 Gy. Conclusions Our study reports the relative improvement in OAR doses per HDR-BT fraction by HDRVOL planning compared to HDRPointA planning and demonstrates the dosimetric advantages of volume-based HDR-BT planning in creating more conformal plans.

Impact of Intensity Modulated Radiation Therapy on Acute Toxicity in Locally Advanced Lung Cancer: Results of a Large Statewide Multi-center Cohort

Secondary analysis of RTOG 0617 has shown lower rates of pneumonitis and less decline in patient quality of life with the use of intensity modulated radiation therapy (IMRT) vs. three-dimensional conformal external beam radiation therapy (3D-CRT) in locally advanced non-small cell lung cancer patients undergoing definitive radiation therapy. In a large statewide radiation oncology quality consortium, we sought to evaluate impact of IMRT vs. 3D-CRT treatment technique on acute esophagitis & pneumonitis.

Radiation Induced Rectal Toxicity

The incidence of late radiation-induced bowel toxicity has been reported to range from 5 to 20 %. Molecularly, NF-KB and COX-2 play important roles in the pathophysiology of radiation induced colitis. Acutely, radiation impairs the proliferative ability of the intestinal mucosa resulting in a deficit in cell re-population while the differentiated cells continue to shed. Chronic radiation injury to the bowel is manifested by a progressive vasculitis leading to thrombosis of small arteries and arterioles resulting in varying degrees of ischemia of the bowel wall. Bleeding is the most common symptom of chronic radiation proctitis compared to acute radiation proctitis where bleeding is relatively uncommon. The classic endoscopic findings of radiation proctitis include prominent telangiectasia, erythema, and friability. In patients receiving high dose rate (HDR) implants for gynecologic malignancies, a higher dose per fraction increases the rate of proctitis. Rectal bleeding was found to correlate with anorectal V55–V65 with V65 being the most significant parameter while stool frequency correlated with anorectal V40.