The impact of pretreatment symptom burden on long-term quality of life following head and neck radiation: A prospective longitudinal study.

BACKGROUND: This study characterized the impact of baseline symptom burden on long-term quality-of-life in patients receiving head and neck radiation therapy (RT). METHODS: The Vanderbilt Head and Neck Symptom Survey was collected prior to head and neck RT and at follow-up visits. Responses were divided into symptom clusters of toxicities and scored from 0 (asymptomatic) to 10 (severe). Patients with responses at baseline and 1-year or 2-year follow-up were stratified by scores ≤1 or >1 and compared using the Mann-Whitney U-test. RESULTS: At 1-year follow-up (n = 75), patients with higher baseline scores had greater symptom burden for every cluster except in taste/smell. At 2-year follow-up (n = 47), patients with higher baseline scores had greater symptom burden for every cluster except in nutrition, dry mouth, trismus, neck tightness, and hearing. CONCLUSION: The Vanderbilt Head and Neck Symptom Survey demonstrated a relationship between baseline symptom burden and long-term quality-of-life and might be useful as a screening tool.

Prolonged response to checkpoint inhibitor therapy in two metastatic mucoepidermoid salivary gland carcinoma cases: a research report.

Salivary gland tumors (SGTs) are heterogeneous tumors that range from benign masses to aggressive high-grade carcinomas with distant metastatic potential and limited response to chemotherapy. Mucoepidermoid carcinoma (MEC) accounts for 10% of SGTs and has a poor prognosis. In this research report, we describe two cases of metastatic high-grade MECs with prolonged response to immune checkpoint inhibitor pembrolizumab. Case 1 presented with a left neck mass, and biopsy of the parotid mass revealed MEC. The patient underwent surgical resection and adjuvant chemoradiation therapy for stage IVB disease. Post-treatment, she was found to have brain and spinal metastases and was placed on pembrolizumab. Case 2 presented with a left neck mass, and biopsy of the right parotid gland revealed MEC. Further staging demonstrated metastatic disease in the lungs, and he was placed on pembrolizumab. Both cases of MEC demonstrated prolonged extracranial responses to pembrolizumab. Although both cases reported little to no PD-L1 expression, these results demonstrate immunotherapy efficacy in advanced/metastatic MEC.

Cutaneous metastasectomy: Is there a role in breast cancer? A systematic review and overview of current treatment modalities.

Cutaneous metastases (CM) are neoplastic lesions involving the dermis or subcutaneous tissues, originating from another primary tumor. Breast cancer is commonest primary solid tumor, representing 24%-50% of CM patients. There is no "standard of care" on management. In particular, the role of surgery in the treatment of cutaneous metastases from breast carcinoma (CMBC) remains controversial. This systematic review evaluates the role of cutaneous metastasectomy in breast cancer and provides an overview of existing treatment types.

Automatic organ contour check: One essential step in autonomous treatment planning.

Geometric and nomenclature errors are commonly encountered in automated treatment planning. We describe a novel algorithm to extract organ geometry relationships from patient structure DICOM data to construct a database that can be used to detect organ contour inaccuracies including relational and naming errors. Twenty-five sets of head and neck patients' treatment plan data (CT, structures) were retrospectively retrieved from our institution. For each dataset, various organs were contoured and verified by experienced physicians. The relative position and orientation between organs were extracted from each patient and the data were used to construct an organ relationship database model. The model was tested using a dataset originating from an in-house organ renaming software that often-introduced organ contour naming mismatches. As part of the validation test, the renamed organs relative positions were compared with the database model to identify mismatches. Within the forty head and neck patients, we extracted the geometric relationship between 201 organ pairs. The average number of unique types of organ pairs (for example, left parotid with left eye is one type of organ pair) stored in the database was 12. Fifteen head and neck structure sets automatically renamed using our in-house organ renaming tool was used as validation data. All of the 30 random assigned wrong name labels present in these structure sets were identified using the established organ geometry relationship database. We successfully constructed a head and neck organ geometry relationship database and validated it in a contour naming quality assurance process. This novel scheme can be expanded to the entire body and shows a great potential in automatic plan physics QA procedure. It should be one essential QA step in an autonomous treatment planning process.

An examination of nationwide trends in accelerated partial breast irradiation - The replacement of breast brachytherapy with intraoperative radiotherapy and external beam radiation.

PURPOSE: To examine recent modality utilization trends in accelerated partial breast irradiation (APBI) in the National Cancer Database (NCDB) based on the American Society for Radiation Oncology (ASTRO) guidelines. MATERIALS AND METHODS: A total of 58,194 patients treated with APBI were identified. Patients were segregated by APBI modality (brachytherapy, external beam radiotherapy [EBRT], and intraoperative radiotherapy ([IORT]). These patients were then further classified by suitability to receive APBI based on ASTRO guidelines. Temporal trends in utilization were evaluated using linear regression. Logistic regression was applied to study factors contributing to APBI modality choice and treatment within the ASTRO suitability groups. RESULTS: Patients treated with brachytherapy, EBRT, and IORT comprised 70.5%, 17.5%, and 12.0% of patients treated with APBI. From 2008 to 2017, total APBI cases remained relatively stable (-54.1 cases/year, p = 0.161) while brachytherapy cases decreased by 258.7 cases/year (p < 0.001). EBRT and IORT increased by 51.5 cases/year (p = 0.019) and 153.1 cases/year (p < 0.001), respectively. 40.0% of patients treated with APBI were classified as "suitable", which increased from 2010 to 2017 from 35.3% to 45.3% (slope = 1.51%/year, r2 = 0.61, p = 0.022). In comparison, 36.0% (36.1% in 2010 to 33.1% in 2017) of patients were classified as "cautionary" (slope = -0.33%/year, r2 = 0.63, p = 0.019) and 23.9% (28.6% in 2010 to 21.6% in 2017) of patients were classified as "unsuitable" (slope = -1.18%/year, r2 = 0.67, p = 0.012). CONCLUSIONS: While overall APBI utilization has remained stable since 2008, this has been accompanied by a decline in brachytherapy and a rise in IORT. The causes of these trends should be the topic of future research.

An Analysis and Comparison of Survival and Functional Outcomes in Oropharyngeal Squamous Cell Carcinoma Patients Treated with Concurrent Chemoradiation Therapy within City of Hope Cancer Center Sites.

Oropharyngeal squamous cell carcinoma (OPSCC) is a subset of head and neck cancers that can arise due to human papillomavirus (HPV) infection. We designed a retrospective analysis to determine differences in outcomes of OPSCC patients treated at City of Hope (COH) Cancer Center's main campus versus selected satellite sites with COH-associated faculty and facilities. Patients diagnosed with OPSCC and treated with concurrent chemoradiation therapy (n = 94) were identified and included in the study. Patients underwent treatment at the COH main campus site (n = 50) or satellite sites (n = 44). The majority of patients were Caucasian, male, and diagnosed with p16 positive stage IV locally advanced OPSCC by AJCC 7th edition. Most patients completed their prescribed cumulative radiation therapy dose and had a complete response to treatment. No significant difference in overall survival and progression-free survival was observed between the main campus and the satellite sites. Our study demonstrates successful treatment completion rates as well as comparable recurrence rates between the main campus and COH-associated satellite sites. A trend toward significant difference in feeding tube dependency at 6-months was observed. Differences in feeding tube placement and dependency rates could be addressed by the establishment of on-site supportive services in satellite sites.

Time to Adjuvant Radiotherapy in Breast Cancer Affects Survival: Implications for the American College of Surgeons Commission on Cancer Quality Metrics.

BACKGROUND: To optimize breast cancer care, the American College of Surgeons Commission on Cancer developed quality measures regarding receipt and timing of adjuvant radiotherapy (RT). Nationwide compliance with these measures and its impact on overall survival (OS) are evaluated herein. PATIENTS AND METHODS: Patients (n = 285,291) diagnosed with invasive breast cancer from 2004 to 2012 were identified from the National Cancer Database. Compliance with RT administration within 365 days from diagnosis was determined for patients with stage III disease with ≥ 4 positive lymph nodes post mastectomy and stage I-III disease post breast-conserving surgery (BCS). Univariate and multivariate logistic regression and Cox proportional hazard models were used to assess factors associated with compliance and OS, respectively. RESULTS: In the mastectomy cohort, 66.9% received timely RT, showing improved OS versus no RT patients (HR 0.70, 95% CI 0.67-0.73). Delayed RT patients (≥ 365 days) achieved equivalent OS to those receiving timely RT (HR 1.07, 95% CI 0.93-1.23) and superior OS to no RT patients (HR 0.74, 95% CI 0.65-0.85). In the BCS cohort, 89.4% received timely RT, showing improved OS versus no RT patients (HR 0.47, 95% CI 0.45-0.49). Delayed RT was associated with improved OS versus no RT (HR 0.64, 95% CI 0.56-0.74) and decreased OS versus timely RT (HR 1.37, 95% CI 1.19-1.58). Factors associated with noncompliance included insurance type and distance to hospital. CONCLUSIONS: Quality measure compliance with adjuvant RT improves OS, regardless of timing after mastectomy. However, timeliness does impact OS after BCS. Focus on modifiable factors to improve compliance such as access to care may lead to improved compliance and OS.

Residual setup errors in cranial stereotactic radiosurgery without six degree of freedom robotic couch: Frameless versus rigid immobilization systems.

PURPOSE AND OBJECTIVES: This IRB-approved study was to compare the residual inter-fractional setup errors and intra-fractional motion of patients treated with cranial stereotactic radiosurgery without a 6 degree of freedom (DoF) couch. We evaluated both frameless non-invasive vacuum-suction immobilization (Aktina PinPoint) and TALON rigid screw immobilization. MATERIALS AND METHODS: Twenty consecutive patients treated by Varian TrueBeam STX or Tomotherapy were selected for data collection. The dose and number of fractions received by each patient ranged from 18 Gy in 1 fraction (SRS) to 25 Gy in 5 fractions (SRT). Twelve patients were immobilized using PinPoint, a frameless suction system (Aktina Medical, New York) and eight patients were immobilized using the TALON rigid screw system. Customized head cushions were used for all patients. Six Atkina patients received pre- and post-treatment cone-beam CT (CBCT) to evaluate the intra-fractional motion of the Aktina system. The intra-fractional motion with the TALON rigid screw system has been reported to be negligible and was not repeated in this study. All patients received pre-treatment CBCT or megavoltage CT (MVCT) to assess inter-fractional setup accuracy. Shifts to the final treatment position were determined based on matching bony anatomy in the pre-treatment setup CT and the planning CT. Setup CT and planning CT were registered retrospectively based on bony anatomy using image registration software to quantify rotational and translational errors. RESULTS: For the frameless Aktina system, mean and standard deviation of the intra-fractional motion were -0.5 ± 0.7 mm (lateral), 0.1 ± 0.9 mm (vertical), -0.5 ± 0.6 mm (longitudinal), -0.04 ± 0.18°(pitch), -0.1 ± 0.23°(yaw), and -0.03 ± 0.17°(roll) indicating negligible intra-fractional motion. Inter-fractional rotation errors were -0.10 ± 0.25° (pitch), -0.08 ± 0.16° (yaw), and -0.20 ± 0.41° (roll) for TALON rigid screw immobilization versus 0.20 ± 0.69° (pitch), 0.34 ± 0.56° (yaw), 0.35 ± 0.82° (roll) for frameless vacuum-suction immobilization showing that the rigid immobilization setup is more reproducible than the frameless immobilization. Without rotational correction by a 6 DoF couch, residual registration error exists and increases with distance from the image fusion center. In a 3D vector space, a tumor located 5 cm from the center of image fusion would require a 0.9 mm margin with the TALON system and a 2.1 mm margin with Aktina. CONCLUSIONS: With image-guided radiotherapy, translational setup errors can be corrected by image registration between pre-treatment setup CT and planning CT. However, rotational errors cannot be accounted for without a 6 DoF couch. Our study showed that the frameless Aktina immobilization system provided negligible intra-fractional motion. The inter-fractional rotation setup error using Aktina was larger than rigid immobilization with the TALON system. To treat a single lesion far from the center of image registration or for multiple lesions in a single plan, additional margin may be needed to account for the uncorrectable rotational setup errors.

Factors predicting for patient refusal of head and neck cancer therapy.

BACKGROUND: The purpose of this study was to evaluate the national rate of treatment refusal in head and neck cancer (HNC). METHODS: The National Cancer Database was queried for nonmetastatic squamous cell carcinoma of the head and neck. Oncologic therapy referred to receipt of surgery, radiotherapy, or chemotherapy. RESULTS: Compared to the 230 424 patients who received treatment, 2965 (1.3%) were reported to have refused definitive therapy. Predictors included older age, female sex, African-American/other race, nonprivate insurance, greater comorbidities, more advanced disease, and residence closer to the treating facility (P < .05). Patients with a prior history of cancer, Hispanic race, those treated at academic centers, and those from higher income counties were less likely to refuse therapy (P < .05). Patients who refused definitive therapy experienced poorer survival (median 79.1 vs 8.7 months, P < .001). CONCLUSIONS: Refusing oncologic therapy is relatively rare in HNC and appears to be multifocal in nature.

Combined modality radiation therapy promotes tolerogenic myeloid cell populations and STAT3-related gene expression in head and neck cancer patients.

Immunomodulation contributes to the antitumor efficacy of the fractionated radiation therapy (RT). Here, we describe immune effects of RT with concurrent systemic cisplatin or cetuximab treatment of patients with stage III-IV head and neck squamous cell carcinoma (HNSCC). Using longitudinally collected blood samples, we identified significant changes in cytokines/chemokines and immune cell populations compared to immune-related gene expression profiles in peripheral blood mononuclear cells (PBMCs). The 7-week combinatorial RT resulted in gradual elevation of proinflammatory mediators (IFNγ, IL-6, TNFɑ, CCL2), while levels of IL-12, cytokine essential for antitumor immune responses, were decreased. These effects correlated with progressive accumulation of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) with detectable activity of STAT3 and PD-L1 expression, underscoring tolerogenic effects of MDSCs. Correspondingly, gene expression analysis of PBMCs harvested after two weeks of combinatorial RT, found upregulation of several immunosuppressive mediators. These included IL6, IL6R, STAT3 and PDL1, which could represent IL-6/STAT3-driven tolerogenic signaling, which inhibits T cell and NK activity. Overall, our results suggest that potential immunostimulatory effects of combinatorial RT in HNSCC patients are likely limited by tolerogenic STAT3 signaling and PD-L1 upregulation in myeloid immune cells. Further studies will clarify whether STAT3 targeting could augment RT efficacy and durability of antitumor responses.

Radiation Therapy for the Head and Neck Patient: Advances, Challenges, and Perspectives.

Radiation therapy for head and neck malignancies has made remarkable advances in treatment technology, resulting in improved clinical and functional outcomes. It is necessary for the radiation oncologist to have a complex understanding of the patient's tumor and its relationship to the surrounding normal anatomy, in order to safely limit dose to normal tissues. Complications following radiation can be managed with timely intervention, usually on an outpatient basis. This chapter will discuss the technological advances in the field, the impact of human papillomavirus (HPV)-mediated disease on radiation treatment, efforts to limit dose to critical salivary and swallowing structures, and management of certain radiation-related toxicities.

Pathologic complete response rates in triple-negative, HER2-positive, and hormone receptor-positive breast cancers after anthracycline-free neoadjuvant chemotherapy with carboplatin and paclitaxel with or without trastuzumab.

BACKGROUND: Pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) is considered a surrogate for improved survival. Platinum-containing NCT, particularly in patients with HER2+ and triple-negative breast cancers (TNBC) may increase pCR rates. METHODS: Tumor characteristics, pCR rates (no invasive disease in breast and lymph nodes), toxicities, and survival in patients who received carboplatin, a taxane, and trastuzumab (HER2+ disease) between April 2009 and December 2011, were reviewed. RESULTS: Thirty eight patients (39 tumors) completed a median of 4 cycles of NCT. Eighteen of 39 (46%) tumors were HER2+, 8/18 (44%) responded with pCR; 13/18 HER2+ tumors were HR+ (72%) and 4/13 (31%) had a pCR. Ten of 39 (26%) tumors were TNBC; 6/10 (60%) had a pCR. At a median of 25-months no recurrences were observed in patients with pCR. CONCLUSIONS: Prospective studies of anthracycline-free platinum-containing NCT are warranted in LABC patients with HER2+ and TNBC.

Effect of CT contrast on volumetric arc therapy planning (RapidArc and helical tomotherapy) for head and neck cancer.

The objectives of the study were to evaluate the effect of intravenous contrast in the dosimetry of helical tomotherapy and RapidArc treatment for head and neck cancer and determine if it is acceptable during the computed tomography (CT) simulation to acquire only CT with contrast for treatment planning of head and neck cancer. Overall, 5 patients with head and neck cancer (4 men and 1 woman) treated on helical tomotherapy were analyzed retrospectively. For each patient, 2 consecutive CT scans were performed. The first CT set was scanned before the contrast injection and secondary study set was scanned 45 seconds after contrast. The 2 CTs were autoregistered using the same Digital Imaging and Communications in Medicine coordinates. Tomotherapy and RapidArc plans were generated on 1 CT data set and subsequently copied to the second CT set. Dose calculation was performed, and dose difference was analyzed to evaluate the influence of intravenous contrast media. The dose matrix used for comparison included mean, minimum and maximum doses of planning target volume (PTV), PTV dose coverage, and V45Gy, V30Gy, and V20Gy organ doses. Treatment planning on contrasted images generally showed a lower dose to both organs and target than plans on noncontrasted images. The doses for the points of interest placed in the organs and target rarely changed more than 2% in any patient. In conclusion, treatment planning using a contrasted image had insignificant effect on the dose to the organs and targets. In our opinion, only CT with contrast needs to be acquired during the CT simulation for head and neck cancer. Dose calculations performed on contrasted images can potentially underestimate the delivery dose slightly. However, the errors of planning on a contrasted image should not affect the result in clinically significant way.

Radiation therapy for breast cancer patients who undergo oncoplastic surgery: localization of the tumor bed for the local boost.

INTRODUCTION: Oncoplastic reconstructive surgery is performed in select patients with breast cancer to allow conservation treatment when the lumpectomy would be expected to have a poor cosmetic outcome. These techniques not only rearrange the breast tissue but may also shift the position of the tumor bed. The oncoplastic incision may have no relationship to the tumor bed. Although use of whole-breast radiation therapy (RT) is straightforward, difficulties in localization of the tumor bed for the local RT boost have not been investigated. MATERIALS AND METHODS: A retrospective review was performed of 25 patients with 26 cancers who received RT after breast conservation surgery with oncoplastic reconstruction. RESULTS: Among 11 patients with a minimum of 4 surgical clips placed at tumor resection, 8 (73%) had the final tumor bed extend beyond the original breast quadrant or be completely relocated into a different region. In 3 (27%) cases, the clinical treatment volume was 2 to 3 separated regions within the breast. DISCUSSION: For breast cancer patients who have had oncoplastic surgery, the tumor bed is frequently more extensive and possibly relocated compared with original presentation. Placement of surgical clips after tumor resection and before oncoplastic reconstruction may be the most accurate method to localize the RT local boost field.

Transarterial radioembolization with Yttrium-90 for regional management of hepatocellular cancer: the early results of a nontransplant center.

Selective arterial radioembolization with Yttrium-90 (Y-90) microspheres has shown promise for regional management of hepatocellular cancer (HCC). Our objective was to report our early experience with this treatment modality from a nontransplant center. Treatment of patients with HCC was discussed in a multidisciplinary tumor board. Patients with unresectable disease resulting from high lesion number, ill location of the tumor, poor hepatic reserve, or medical comorbidities were offered Y-90 treatment. Liver treatment was either lobar or tumor-targeted. Response to therapy was assessed by CT scan obtained within 3 months using Response Evaluation Criteria in Solid Tumors criteria. During 2007 to 2009, 40 Y-90 radioembolizations were performed in 20 patients with age that ranged from 16 to 87 years; four patients were 80 years old or older. After the first therapy, CT assessment of the treated area showed stable disease (n=15), partial response (n=3), and progression (n=2). Of the two patients who progressed, one was retreated with a subsequent complete response. The other patient died of progressive disease. The most common side effects were mild fatigue, anorexia, and nausea. In summary, our nontransplant center experience shows that Y-90 radioembolization is a well-tolerated treatment in select patients with unresectable HCC with an associated high rate of local tumor control.

Prognostic significance of bone or cartilage invasion of locally advanced head and neck cancers.

PURPOSE/OBJECTIVE(S): Locally advanced squamous cell cancers of the head and neck with bone and cartilage invasion (BCI) traditionally have been treated with resection followed up with radiotherapy or less commonly definitive chemoradiotherapy (CRT). However, it is unclear whether bone or cartilage invasion confers a worse prognosis in comparison with each other. MATERIALS/METHODS: T4N0-3M0 squamous cell cancers of the head and neck patients underwent CRT or radical resection followed up with postoperative CRT. Oral cavity, oropharynx, laryngeal and hypopharyngeal squamous cell cancers were included. Radiotherapy ranged from 59.4 to 72 Gy. Concurrent chemotherapy was platinum based. RESULTS: Forty-six patients with BCI were treated. When treated with CRT, 5-year local control was 55% and 43% for BCI, respectively (P = 0.23). Five-year overall survival for these patients was 54% and 29% for BCI, respectively (P = 0.99). When treated with upfront resection, 5-year local control was not significantly different (P = 0.60) nor was 5-year overall survival (P = 0.15). CONCLUSIONS: This study suggests similar outcomes between patients with bone or cartilage invasion treated with upfront CRT or resection followed by CRT. Concurrent CRT may be viable alternative to resection in patients with either bone or cartilage invasion.

Treatment outcomes of T4 locally advanced head and neck cancers with soft tissue invasion or bone and cartilage invasion.

PURPOSE/OBJECTIVE(S): T4 locally advanced squamous cell cancers of the head and neck (SCCHN) with bone and cartilage invasion (BCI) traditionally have been treated with resection followed up with chemoradiotherapy (CRT). Because the organ preservation trials, more patients with BCI, as well as those with soft tissue invasion (STI), have been treated with definitive CRT. This is a review of our experience. MATERIALS/METHODS: We performed a retrospective review of patients who underwent definitive CRT or radical resection followed up with postoperative CRT for T4N0-3M0 locally advanced SCCHN. We analyzed outcomes based on STI/BCI and types of treatment. Radiotherapy doses ranged from 59.4 to 72 Gy. Concurrent chemotherapy was platinum based in all CRT patients. RESULTS: From 1995 to 2006, 101 patients with locally advanced SCCHN were treated definitively. Of these, 51 had STI and 50 had BCI. Of the 51 patients with STI, 42 were treated with CRT, 5 patients were treated with resection followed by CRT, and 4 patients were treated with radiotherapy alone. Of the 50 patients with BCI, 26 patients were treated with CRT, 20 patients were treated with radical resection followed by radiotherapy or CRT, and 4 patients were treated with radiotherapy alone. Five-year local-regional control was 51% and 43% for STI and BCI patients treated with CRT, respectively, and 44% for BCI treated with radical resection. Five-year overall survival was 23%, 51%, and 28% for STI treated with CRT, BCI treated with CRT, and BCI treated with radical resection. Outcomes were not statistically different between these groups. CONCLUSIONS: This study suggests similar outcomes for CRT or resection followed up with chemoradiotherapy for patients with locally advanced SCCHN with BCI. Concurrent CRT may be viable alternative to upfront resection in these patients. Further studies should be performed to validate these provocative findings.

Human papillomavirus infection as a prognostic factor in oropharyngeal squamous cell carcinomas treated in a prospective phase II clinical trial.

UNLABELLED: The aim of this study was to determine the presence of high-risk HPV-16 in patients with HNSCC, assess the impact of HPV status on treatment response and survival in this select cohort treated with combined modality therapy and to identify the differences in HIF-1alpha and VEGF expression in HPV-positive and -negative tumors. PATIENTS AND METHODS: Patients had resectable, untreated stage III, IV HNSCC of the oral cavity, oropharynx, hyopharynx or larynx, and stage II cancer of the base of tongue, hypopharynx and larynx. HPV status was determined by conventional PCR in fresh frozen biopsy samples and by Taqman PCR assay on formalin-fixed, paraffin-embedded specimens. HIF-1alpha and VEGF expression were assessed by quantitative real-time PCR (RT-PCR). Multivariate Cox proportional hazards regression analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) based on HPV status. RESULTS: HPV-16 was detected in 14 of 24 evaluable cases. There were no significant differences in response rates after neoadjuvant chemotherapy (86% vs. 90%) in HPV-positive and HPV-negative patients, respectively. There was a trend toward better progression-free (HR=0.15, 95% CI=0.002-12.54; p=0.06) and overall survival (HR=0.14, 95% CI=0.001-14.12; p=0.10) for HPV-positive patients. In a subset of 13 fresh frozen samples, RT-PCR revealed a significant increase in VEGF mRNA levels in HPV-positive tumors (p<0.01). No difference was seen for HIF-1alpha expression. CONCLUSION: HPV presence portended a better prognosis in patients with oropharyngeal SCC treated with a multimodality treatment in a prospective clinical trial. The level of VEGF mRNA was up-regulated in HPV-16-positive tumors possibly through an HIF-1 independent manner.

Setup variations in radiotherapy of esophageal cancer: evaluation by daily megavoltage computed tomographic localization.

PURPOSE: To use pretreatment megavoltage computed tomography (MVCT) scans to evaluate setup variations in anterior-posterior (AP), lateral, and superior-inferior (SI) directions and rotational variations, including pitch, roll, and yaw, for esophageal cancer patients treated with helical tomotherapy. METHODS AND MATERIALS: Ten patients with locally advanced esophageal cancer treated by combined chemoradiation using helical tomotherapy were selected. After patients were positioned using their skin tattoos/marks, MVCT scans were performed before every treatment and automatically registered to planning kilovoltage CT scans according to bony landmarks. Image registration data were used to adjust patient setups before treatment. A total of 250 MVCT scans were analyzed. Correlations between setup variations and body habitus, including height, weight, relative weight change, body surface area, and patient age, were evaluated. RESULTS: The standard deviations for systematic setup corrections in AP, lateral, and SI directions and pitch, roll, and yaw rotations were 1.5, 3.7, and 4.8 mm and 0.5 degrees, 1.2 degrees, and 0.8 degrees, respectively. The appropriate averages of random setup variations in AP, lateral, and SI directions and pitch, roll, and yaw rotations were 2.9, 5.2, and 4.4 mm, and 1.0 degrees, 1.2 degrees, and 1.1 degrees, respectively. Setup variations were stable throughout the entire course of radiotherapy in all three translational and three rotational displacements, with little change in magnitude. No significant correlations were found between setup variations and body habitus variables. CONCLUSIONS: Daily MVCT scans before each treatment can effectively detect setup errors and thereby reduce planning target volume (PTV) margins. This will reduce radiation dose to critical organs and may translate into lower treatment-related toxicities.