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Although rare, the rate of squamous cell carcinoma of the anus (SCCA) is rising globally. Most patients present with nonmetastatic disease and are curable with appropriate treatment, which has evolved significantly over the last several decades. Before the 1970s, SCCA was managed with radical surgery, resulting in a permanent colostomy. Researchers found that preoperative treatment with chemotherapy and concurrent radiation could achieve a pathologic complete response. After this observation, definitive therapy shifted from radical surgery to sphincter-preserving chemoradiation. Investigations into the necessity of chemotherapy and the optimal regimen found that chemotherapy with mitomycin-C and 5-fluorouracil is required for cure. Further studies evaluating the addition of induction or maintenance chemotherapy, monoclonal antibody therapy, or higher radiation doses have demonstrated no significant benefit to disease control. Advanced radiation delivery with intensity-modulated radiotherapy techniques is now considered the standard of care because of its prospectively determined, favorable acute toxicity profile compared with 3-dimensional conformal radiation. It is important to note that chemoradiation treatment response may be slow (up to 26 weeks) and should be assessed through serial clinical examinations. Today, surgical management of SCCA is reserved only for the lowest risk, early stage tumors or for recurrent/persistent disease. Current studies are evaluating radiation dose de-escalation in early stage disease and radiation dose escalation and the addition of immune checkpoint inhibitors in locally advanced cancers. In reviewing how and why modern-day treatment of SCCA was established, the objective of this report is to reenforce adherence to current treatment paradigms to assure the best possible outcomes for patients.

BACKGROUND Chemoradiation with 5-fluorouracil and mitomycin remains the standard of care for squamous cell carcinoma (SCC) of the anal canal. A prolonged treatment time is associated with inferior disease-specific outcomes. Radiation Therapy Oncology Group trial 0529 demonstrated decreased toxicity and fewer treatment breaks with intensity-modulated radiotherapy (IMRT), but this has not been assessed in a randomized trial. Using data from the National Cancer Data Base (NCDB), this study evaluated the impact of IMRT on treatment time and survival in anal SCC. METHODS The NCDB was used to identify patients with anal cancer from 2004 to 2013. The included patients were those with stage I to III squamous cell cancer of the anal canal who had received definitive chemoradiation by IMRT or 3-dimensional conformal radiation therapy (3DCRT). Statistical analyses were performed with logistic regression, Kaplan-Meier analysis, Cox proportional hazards analysis, and propensity score-matched analysis. RESULTS Of 6814 patients, 57.4% were treated with 3DCRT, whereas 42.6% received IMRT. Patients receiving IMRT had a reduced risk of a long treatment time in a multivariate analysis (P < .001). The 5-year overall survival (OS) rates with IMRT and 3DCRT were 80.8% and 78.9%, respectively (P = .0036). According to a propensity analysis, patients receiving IMRT had improved OS (P = .039) and a reduced risk of a long treatment time (P < .0001) in a multivariate analysis. CONCLUSIONS IMRT use was associated with significantly reduced overall treatment time and improved survival in comparison with 3DCRT. It is important to note that NCDB data are not as robust as randomized data. However, these results further support the use of IMRT as part of sphincter-preserving therapy for the anal canal.

Background The purpose of this study was to evaluate how gross tumor volume (GTV) affects treatment outcome among different race/ethnic groups in patients with head and neck cancer receiving definitive radiotherapy (RT). Methods Ninety-one patients with head and neck cancer were treated to a median RT dose of 69.96 Gy in 33 fractions. The patient's self-reported race/ethnicity, primary tumor, and nodal GTV were obtained. Two-year actuarial local, nodal, and distant control, and overall and disease-free survival were calculated. Results The patients were categorized as white (n = 43) or non-white (n = 48), which included 29 African Americans, 11 Hispanics, 5 Asians, and 3 others. The mean primary GTV was 21.0 cc and 39.9 cc for whites and non-whites, respectively (p = .011). White patients reported improved overall survival of 85.4% compared to non-whites (65.8%; p = .006). Improvements in local and nodal control and disease-free survival rates were also observed. Conclusion White patients demonstrated improved treatment outcomes compared with non-whites, which may be reflective of tumor volume. © 2014 Wiley Periodicals, Inc. Head Neck, 2015

BACKGROUND: The Radiation Therapy Oncology Group (RTOG) trial 97-14 revealed no difference between radiation delivered for painful bone metastases at a dose of 8 gray (Gy) in 1 fraction (single-fraction radiotherapy [SFRT]) and 30 Gy in 10 fractions (multifraction radiotherapy [MFRT]) in pain relief or narcotic use 3 months after randomization. SFRT for painful vertebral bone metastases (PVBM) has not been well accepted, possibly because of concerns about efficacy and toxicity. In the current study, the authors evaluated the subset of patients that was treated specifically for patients with PVBM. METHODS: PVBM included the cervical, thoracic, and/or lumbar spine regions. Among patients with PVBM, differences in retreatment rates and in pain relief, narcotic use, and toxicity 3 months after randomization were evaluated. RESULTS: Of 909 eligible patients, 235 (26%) had PVBM. Patients with and without PVBM differed in terms of the percentage of men (55% vs 47%, respectively; P = .03) and the proportion of patients with multiple painful sites (57% vs 38%, respectively; P < .01). Among those with PVBM, more patients who received MFRT had multiple sites treated (65% vs 49% for MFRT vs SFRT, respectively; P = .02). There were no statistically significant treatment differences in terms of pain relief (62% vs 70% for MFRT vs SFRT, respectively; P = .59) or freedom from narcotic use (24% vs 27%, respectively; P = .76) at 3 months. Significant differences in acute grade 2 through 4 toxicity (20% vs 10% for MFRT vs SFRT, respectively; P = .01) and acute grade 2 through 4 gastrointestinal toxicity (14% vs 6%, respectively; P = .01) were observed at 3 months, with lower toxicities seen in the patients treated with SFRT. Late toxicity was rare. No myelopathy was recorded. SFRT produced higher 3-year retreatment rates (5% vs 15%; P = .01). CONCLUSIONS: Results for the subset of patients with PVBM in the RTOG 94-17 randomized controlled trial were comparable to those for the entire population. SFRT produced less acute toxicity and a higher rate of retreatment than MFRT. SFRT and MFRT resulted in comparable pain relief and narcotic use at 3 months. Cancer 2013. © 2012 American Cancer Society.

Neoadjuvant chemotherapy and radiation are being utilized with increasing frequency in the multimodal treatment of esophageal cancer, although their effects on morbidity, mortality, and survival remain unclear. The objective of this study was to determine the outcome of multimodal treatment in patients with localized esophageal cancer treated at a single institution. Between 1995 and 2002, 118 patients underwent treatment for localized esophageal cancer, utilizing surgery alone, chemoradiation alone, or surgery following neoadjuvant chemoradiation. There was no statistically significant difference in morbidity, mortality, or length of stay between the patients who received multimodal therapy when compared to surgery alone. A surgical resection after down-staging was possible in 9 out of 28 patients (32%) with a clinically non-resectable tumor (T4 or M1a). Forty-seven percent of the patients who received neoadjuvant therapy had a complete pathologic response with a 3-year survival of 59% as compared to only 20 months in those patients who did not achieve a complete response (P = 0.037). Neoadjuvant chemotherapy administered concomitantly with conformal radiotherapy can be performed safely in the treatment of esophageal cancer, without increasing the operative morbidity, mortality, or length of stay. The higher complete response rates to neoadjuvant treatment (as compared to other reports) may be due to the use of three-dimensional conformal radiation therapy or the novel use of weekly carboplatin and paclitaxel.

Purpose: To measure the CT density model variations between different CT scanners used for treatment planning and impact on the accuracy of MC dose calculation in lung SBRT. Methods: A Gammex electron density phantom (RMI 465) was scanned on two 64-slice CT scanners (GE LightSpeed VCT64) and a 16-slice CT (Philips Brilliance Big Bore CT). All three scanners had been used to acquire CT for CyberKnife lung SBRT treatment planning. To minimize the influences of beam hardening and scatter for improving reproducibility, three scans were acquired with the phantom rotated 120° between scans. The mean CT HU of each density insert, averaged over the three scans, was used to build the CT density models. For 14 patient plans, repeat MC dose calculations were performed by using the scanner-specific CT density models and compared to a baseline CT density model in the base plans. All dose re-calculations were done using the same plan beam configurations and MUs. Comparisons of dosimetric parameters included PTV volume covered by prescription dose, mean PTV dose, V5 and V20 for lungs, and the maximum dose to the closest critical organ. Results: Up to 50.7 HU variations in CT density models were observed over the baseline CTmore » density model. For 14 patient plans examined, maximum differences in MC dose re-calculations were less than 2% in 71.4% of the cases, less than 5% in 85.7% of the cases, and 5–10% for 14.3% of the cases. As all the base plans well exceeded the clinical objectives of target coverage and OAR sparing, none of the observed differences led to clinically significant concerns. Conclusion: Marked variations of CT density models were observed for three different CT scanners. Though the differences can cause up to 5–10% differences in MC dose calculations, it was found that they caused no clinically significant concerns.« less

Purpose: Standard quality assurance of Varian's trilogy frameless‐stereotactic radiotherapy(SRT) relies on the a match between the system's optical isocenter and room lasers. It does not match the static kV isocenter of the On‐Board‐Imaging(OBI) or the dynamic kV isocenter of the CBCT, nor does it QA the MV isocenter. Our purpose was to establish a quality assurance(QA) procedure for all isocenters including the MV isocenter for frameless‐SRT. Method and Materials: An acrylic phantom with dimensions of 15×15×15 cm3 was constructed. The phantom included a removable slab that contains two machined holes designed to hold a stainless‐steel ball‐bearing(BB). One machined hole is at the center of the cube, and another is off to one side to established phantom orientation during scanning. The BB is removed during CBCTimaging to minimize artifacts and is replaced for kV and MV images. The Trilogy frameless‐SRT array is mounted atop of the phantom and it is positioned at the LINAC isocenter. Repeated CB‐3D, 2D‐OBI datasets were acquired to determine the system's ability to detect and correct for known table shifts. All shifts observed and recovered by the SRT system were tabulated. Each recovered shift was verified by a Winston‐Lutz(WL) test. The differences between known shift, OBI, CBCT, SRT and the WL test were recorded and tabulated. The couch's ability to recover to a known initial position was also tested and tracked by SRT camera system. Results and Conclusion: Initial results showed the couch had a precision of

Purpose: In accelerated partial breast irradiation (APBI), accurate localization of the lumpectomy cavity is important. We are investigating daily localization of the lumpectomy cavity in patients with implanted surgical clips by kV imaging followed by conebeam CT(CBCT). Initial data based on 2 patients are presented here. Target registration error (TRE) analysis was performed to assess the accuracy of available image‐guidance techniques for target localization during APBI. Method and Materials: APBI patients were positioned to the treatment isocenter initially by laser alignment to skin tattoos, followed by orthogonal kV radiographs to visualize bony anatomy and surgical clips and then by CBCT (once daily) to visualize both surgical clips and soft tissue architecture. Couch shifts were performed based on matching surgical clip position and lumpectomy cavity architecture (when visible) to the planned setup. The lumpectomy cavity position was assumed to be represented by the surgical clips. The TRE is defined as the residual setup error following isocenter alignment. Surface topologyanalysis on the serial CBCT datasets was performed post‐treatment by co‐registering the breast surfaces, as defined by CBCT, and then measuring the clip misalignment. Results: The average laser setup TREs (determined by kV imaging) for patients 1 (breast volume = 1335.5cc) and 2 (breast volume = 404.7cc) were 3.7mm and 6.1mm, respectively. The average kV imaging TREs (determined by CBCT, post‐kV imaging shifts) for patients 1 and 2 were 4.9mm and 1.4mm, respectively. The average surface topology TREs for patients 1 and 2 were 4.9mm and 1.6mm, respectively. Conclusion: Even after kV imaging, TREs around 0.5cm were detected using CBCT in the larger breast volume. Therefore, CBCT may improve targeting in APBI for patients with large breast volumes. Surface alignment may be more suitable for patients with small breast volumes and is currently under further investigation.