E.F. Crandley

Treatment‐related complications of radiation therapy after radical prostatectomy: comparative effectiveness of intensity‐modulated versus conformal radiation therapy

Intensity‐modulated radiation therapy (IMRT) is frequently utilized after prostatectomy without strong evidence for an improvement in outcomes compared to conformal radiation therapy (RT). We analyzed a large group of patients treated with RT after radical prostatectomy (RP) to compare complications after IMRT and CRT. The Surveillance, Epidemiology and End Results (SEER)‐Medicare database was queried to identify male Medicare beneficiaries aged 66 years or older who underwent prostatectomy with 1+ adverse pathologic features and received postprostatectomy RT between 1995 and 2007. Chi‐square test was used to compare baseline characteristics between the treatment groups. First complication events, based upon administrative procedure or diagnosis codes occurring >1 year after start of RT, were compared for IMRT versus CRT groups. Propensity score adjustment was performed to adjust for potential confounders. Multivariable Cox proportional hazards models of time to first complication were performed. A total of 1686 patients were identified who received RT after RP (IMRT = 634, CRT = 1052). Patients treated with IMRT were more likely to be diagnosed after 2004 (P < 0.001), have minimally invasive prostatectomy (P < 0.001) and have positive margins (P = 0.019). IMRT use increased over time. After propensity score adjustment, IMRT was associated with lower rate of gastrointestinal (GI) complications, and higher rate of genitourinary‐incontinence complications, compared to CRT. The observed outcomes after IMRT must be considered when determining the optimal approach for postprostatectomy RT and warrant additional study.

Prognostic Significance of p16 and Its Relationship With Human Papillomavirus in Pharyngeal Squamous Cell Carcinomas

IMPORTANCE The prognostic significance of p16 in squamous cell carcinoma (SCC) of the hypopharynx (HP) and nasopharynx (NP) and relationship between human papillomavirus (HPV) and p16 is unclear. OBJECTIVES To evaluate the prognostic significance of p16 in pharyngeal subsites (oropharynx [OP], HP, and NP) and assess the relationship between HPV and p16 in the HP and NP. DESIGN, SETTING, AND PARTICIPANTS Retrospective medical record review of 172 patients with SCC of the pharynx treated with definitive radiation therapy from 2002 to 2013 at a university tertiary referral center, with tissue available for immunohistochemical analysis. The median follow-up was 30.1 months. INTERVENTIONS A total of 118 patients were treated with chemoradiation, and 54 patients were treated with radiation alone. Immunohistochemical analysis for p16 was performed for all tumors. Hypopharynx and NP tumors were tested for HPV using in situ hybridization, and NP tumors were tested for Epstein-Barr virus. MAIN OUTCOMES AND MEASURES Overall survival, locoregional control, and disease-free survival were analyzed according to p16, HPV, and Epstein-Barr virus status. RESULTS Thirty-two patients had HP SCC, 127 had OP SCC, and 13 had NP SCC. p16 Was positive in the HP (34%), OP (66%), and NP (46%). Prevalence of HPV was 14% in the HP and 50% in the NP. As a test for HPV, p16 had a positive predictive value of 38% (HP) and 67% (NP) and a negative predictive value of 100% in HP and NP tumors. p16 Status was a significant predictor of all clinical outcomes for patients with OP SCC (P<.001), but not for patients with HP or NP SCC. Patients with Epstein-Barr virus- or HPV-associated NP SCC had improved clinical outcomes. CONCLUSIONS AND RELEVANCE p16 Was not associated with improved outcomes in patients with HP or NP SCC. The positive predictive value of p16 as a test for HPV is too low for p16 testing alone in the HP and NP. However, p16 negativity is sufficient to rule out HPV. As a research approach, we recommend p16 immunohistochemistry as a screening test for HPV in NP SCC and HP SCC followed by confirmatory HPV in situ hybridization when p16 positive.

Patterns of Distant Failure and Second Primary Cancers in Patients with Oropharyngeal Squamous Cell Carcinoma: Implications for Surveillance Methodology

Background: We analyzed the pattern of distant metastasis (DM) and secondary primary cancers (SPC) in patients with oropharyngeal squamous cell carcinoma (OPSCC) to develop surveillance guidelines. Methods: A retrospective review of 177 patients with OPSCC treated with intensity modulated radiation therapy ± chemotherapy between 2002 and 2012 was performed to characterize the rate, pattern, and timing of DM and SPC. Results: Sixteen patients (9.0%) developed DM and 9 patients (5.1%) developed a SPC. Overall, 24/177 patients (13.6%) developed a DM and/or SPC for a total of 27 events. 92.6% (25/27) of events were detectable on physical exam and/or chest CT. p16+ patients developed DM later than p16- tumors (23.4 months versus 8.7 months). Conclusions: Chest CT with physical examination detects the majority of DM and SPC in patients with OPSCC and would provide effective surveillance in these patients. A risk adapted surveillance strategy is proposed.

SU‐E‐T‐427: Effect of Contrast in Radiadyne Alatus Balloon Packing System on Bladder and Rectal Doses in Gynecological Brachytherapy

PURPOSE Vaginal packing for gynecological brachytherapy is used to immobilize the applicator and reduce doses to the bladder and rectum by increasing the separation from the applicator. With the introduction of theRadiadyne Alatus™ balloon packing system, we evaluate further reductions in dose to these structures by increasing the concentration of contrast in the balloon, increasing its attenuation. This evaluation has been performed using the Acuros™ dose calculation algorithm. METHODS A patient with cervical cancer was treated with HDR Ir-192 by insertion of a tandem and ovoid applicator, with the Alatus™ balloon system used for vaginal packing instead of wet gauze. The balloons were filled with distilled water containing 10% Omnipaque contrast. Retrospectively, the balloons were contoured in the BrachyVision™ planning system, and the CT number of the structure set was adjusted to determine the effect of the concentration of the contrast in the balloons on bladder and rectal doses after heterogeneity correction using the Acuros™ algorithm. RESULTS Use of 10% Omnipaque solution reduced the bladder and rectal point doses by 6% and 9.5%, respectively, with similar reductions in the D2cc and D1cc for each structure. Overriding the density of the balloon showed that a 50% solution would reduce the doses by 8% and 30%, respectively, due to the positions of the balloons with respect to the applicator dwell positions. CONCLUSIONS Use of the Alatus™ balloon packing system allows reduction of the bladder and rectal doses both by increasing the distance between the bladder and rectum and the applicators and by increased attenuation of the dose by the use of contrast solution. Optimal dilution of the contrast should take into account both the positive protective effect of the solution as well as any negative artifact that the solution causes in the CT scan, which might obscure the patients anatomy patient.

SU‐E‐J‐36: Accuracy of MRI/CT Registration for Spinal SBRT Target Definition

Purpose: To quantify the uncertainties in imaging registration for treatment of spinal SBRT by tomotherapy. The uncertainties are quantified for kilovoltage computed tomography/magnetic resonance imaging (kVCT/MRI) and then kVCT/megavotage CT (MVCT) in a two‐step procedure. Methods: Spinal MRI and kVCT and MVCT images for 11 patients were imported to VelocityAIS software, which can perform automated and manual rigid registration between different imaging modalities. Gross tumor volume (GTV) and spinal cord were contoured on MRI.Image registration of MRI and kVCT favoring GTV was repeated for 2 times for each patient. GTV and cord were then mapped to kVCT, giving GTVmap1, GTVmap2, cordmap1, and cordmap2. GTVmap1 is then expanded isotropically by 1mm 2mm 3mm and 4mm until the expanded volume encompasses GTVmap2. Similarity of the contours is defined by Dice index, ratio of overlapping volume of the contours from two registrations to the original volume. kVCT/MVCT registrations were then performed. Contours were mapped to MVCT. Dice index was then calculated.Results: For repetitive MRI/kVCT registrations, manual registration was always required to improve the accuracy, resulting in average Dice index of 0.81±0.08 for cord and 0.91±0.04 for GTV between different trials. Most patients require 2mm expansion in order to compensate for the difference between the two repetitive MRI/KVCT registrations, indicating the reproducibility of the registration has a 2mm uncertainty for GTV. Compared to the kVCT/MRI registration, kVCT/MCVT registration can be performed reproducibly with automated registration, resulting in close to 100% Dice index and 0 uncertainties Conclusions: An intrinsic 2mm error was observed for MRI/KVCT registration but not between the kVCT and MVCT. The results indicate the necessity of taking the 2 mm uncertainties into consideration in contour transfer from MRI to CT.