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Radiopharmaceutical therapy (RPT) is an area of projected growth and importance with several agents in clinical use, new agents in late-phase clinical trials, and many others under testing and development. This article proposes a framework for developing pathways of care that can be broadly applied to all RPTs, representing the current status of RPT. It suggests foundational elements for many pathways of care for patients with cancer and concludes with areas in active development and the future horizon for RPT treatment centers. Developing a framework for patient-centered pathways of care is a critical step in establishing RPT as standard therapy for patients with a diverse spectrum of cancers. This expected increase in RPT treatment options will affect a much larger population of patients with complex cancer. It will also require enhanced coordination and collaboration among appropriately qualified personnel with diverse expertise in image acquisition, image interpretation, quantitative imaging, dosimetry calculation, radiation quality assurance and safety as well as oncology care and RPT-induced sequelae and response assessment. The essential role of this evolving RPT care team within multidisciplinary oncology care is a cornerstone of this framework for a patient-centered pathway of care for RPT. Given the status of current RPT practice and the horizon for future applications, this patient-centered pathway of care guidance is timely and should help inform future clinical RPT practice paradigms. A task force was recruited from the Theranostic Working Group of the American Society for Radiation Oncology (ASTRO) in May 2019 with equal representation from the nuclear medicine community. The task force expanded on a framework that was originally conceived by the Working Group for patient-centered care. This framework was developed to incorporate the strengths of both radiation oncologists and nuclear medicine physicians. The manuscript was then developed by the task force and posted on the ASTRO website for a 6-week public comment period ending in July 2020. Comments were adjudicated, and the draft was sent to external organizations for potential endorsement. This document was sent to the ASTRO Board of Directors in October 2020 for approval. [ABSTRACT FROM AUTHOR]

Abstract Purpose The number of studies that evaluate treatment margins for high grade gliomas (HGG) are limited. We hypothesize that patients with HGG who are treated with a gross tumor volume (GTV) to planning tumor volume (PTV) expansion of ≤1 cm will have progression-free survival (PFS) and overall survival (OS) rates similar to those treated in accordance with standard protocols by the Radiation Therapy Oncology Group or European Organisation for Research and Treatment of Cancer. Furthermore, the PFS and OS of subgroups within the study population will have equivalent survival outcomes with GTV1-to-PTV1 margins of 1.0 cm and 0.4 cm. Methods and materials Treatment plans and outcomes for patients with pathologically confirmed HGG were analyzed (n = 267). Survival (PFS and OS) was calculated from the time of the first radiation treatment and a χ2 test or Fisher exact test was used to calculate the associations between margin size and patient characteristics. Survival was estimated using Kaplan-Meier and compared using the log-rank test. All analyses were performed on the univariate level. Results The median PFS and OS times were 10.6 and 19.1 months, respectively. By disease, the median PFS and OS times were 8.6 and 16.1 months for glioblastoma and 26.7 and 52.5 months for anaplastic glioma. The median follow-up time was 18.3 months. The treatment margin had no effect on outcome and the 1.0 cm GTV1-PTV1 margin subgroup (n = 212) showed median PFS and OS times of 10.7 and 19.1 months, respectively, and the 0.4 cm margin subgroup (n = 55) 10.2 and 19.3 months, respectively. In comparison with the standard treatment with 2 cm to 3 cm margins, there was not a significant difference in outcomes. Conclusions There is no apparent difference in survival when utilizing smaller versus larger margins as defined by the guidelines of the Radiation Therapy Oncology Group and European Organisation for Research and Treatment of Cancer. Although there remains no class I evidence that outcomes after treatment with smaller margins are identical to those after treatment with larger margins, this large series with long-term follow up suggests that a reduction of the margins is safe and further investigation is warranted. [ABSTRACT FROM AUTHOR]

The growth of functional and metabolically informative imaging is eclipsing anatomic imaging alone in clinical practice. The recognition that magnetic resonance (MR) and positron emission tomography (PET)-based treatment planning and response assessment are essential components of clinical practice and furthermore offer the potential of quantitative analysis being important. Extracting the greatest benefit from these imaging techniques will require refining the best combinations of multimodality imaging through well-designed clinical trials that use robust image-analysis tools and require substantial computer based infrastructure. Through these changes and enhancements, image-based biomarkers will enhance clinical decision making and accelerate the progress that is made through clinical trial research. [Copyright &y& Elsevier]

Purpose: The aim of this study was to determine the optimal number of coplanar and noncoplanar external beams in the setting of stereotactic body radiotherapy (SBRT). Methods and Materials: Spherical targets were delineated within 2 separate extracranial sites, the lung and liver, with diameters varying from 2 cm to 7 cm to cover the range of volumes used in SBRT. Treatment plans were created for all target volumes using 5 to 15 geometrically optimized coplanar and noncoplanar conformal beams. Dose gradient and normal tissue complication probability (NTCP) were evaluated for each set of beam configurations and for each target size. Results: For all lung and liver target volumes, the dose gradient improved with an increase in beam number from 5 to 15 for both coplanar and noncoplanar beam configurations. NTCP decreased as the beam number increased from 5 to 9 beams for all target sizes for both coplanar and noncoplanar beams. There is no significant improvement in NTCP when more than 9 beams were used for treatment planning regardless of target size. Conclusion: Based on dosimetric criteria, the optimal number of external beams is 13 to 15 for SBRT using either coplanar or noncoplanar beam bouquets. Simple biologic models indicate that the optimal number of beams is 9 for SBRT of lung and liver lesions >2 cm, whereas smaller lesions may benefit from plans using up to 13 beams. [Copyright &y& Elsevier]

Optical tracking determines an object’s position by measuring light either emitted or reflected from the object. The hallmark of optical tracking systems is their high spatial resolution and measurement in real time; such systems can resolve the position of a point source within a fraction of a millimeter and report at a rate of 10 Hz or faster. Several systems have been developed for radiation therapy, all of which track infrared markers attached to the patient’s external surface. The positions of the optical markers relative to the target volume, together with the desired marker positions relative to treatment isocenter, are determined during computed tomography simulation. In the treatment room, the real marker positions are measured relative to isocenter; rigid-body mathematics then determine marker displacements from their desired positions and hence target displacement from isocenter. Real-time feedback allows one to correct the patient’s position. The first systems were used for intracranial stereotaxis radiotherapy; rigid arrays of optical markers were attached to the patient via a biteplate linkage. Subsequent systems for extracranial radiotherapy tracked external markers to determine patient position and/or gate the radiation beam based on patient motion. Lastly, optical tracking has been integrated with ultrasound or stereoscopic x-ray imaging to determine the position of internal anatomy targets relative to isocenter. [Copyright &y& Elsevier]

Purpose: Stereotactic radiosurgery is an effective treatment modality for many intracranial lesions, but target mobility limits its utility for extracranial applications. We have developed a new technique for extracranial radiosurgery based on optically guided three-dimensional ultrasound (3DUS). The 3DUS system provides the ability to image the target volume and critical structures in real time and determine any misregistration of the target volume with the linear accelerator. In this paper, we describe the system and its initial clinical application in the treatment of localized metastatic disease.Methods and Materials: The extracranial stereotactic system consists of an ultrasound unit that is optically tracked and registered with the linear accelerator coordinate system. After an initial patient positioning based on computed tomographic (CT) simulation, stereotactic ultrasound images are acquired and correlated with the CT-based treatment plan to determine any soft-tissue shifts between the time of the planning CT and the actual treatment. Optical tracking is used to correct any patient offsets that are revealed by the real-time imaging.Results: Preclinical testing revealed that the ultrasound-based stereotactic navigation system is accurate to within 1.5 mm in comparison with an absolute coordinate phantom. Between March 2001 and March 2002, the system was used to deliver extracranial radiosurgery to 17 metastatic lesions in 16 patients. Treatments were delivered in 1 or 2 fractions, with an average fractional dose of 16 Gy (range 12.5-24 Gy) delivered to the 80% isodose surface. Before each fraction, the target misalignment from isocenter was determined using the 3DUS system and the misalignments averaged over all patients were anteroposterior = 4.8 mm, lateral = 3.6 mm, axial = 2.1 mm, and average total 3D displacement = 7.4 mm (range = 0-21.0 mm). After correcting patient misalignment, each plan was delivered as planned using 6-11 noncoplanar fields. No acute complications were reported.Conclusions: A system for high-precision radiosurgical treatment of metastatic tumors has been developed, tested, and applied clinically. Optical tracking of the ultrasound probe provides real-time tracking of the patient anatomy and allows computation of the target displacement before treatment delivery. The patient treatments reported here suggest the feasibility and safety of the technique. [ABSTRACT FROM AUTHOR]

This paper is the first of a Series on theranostics that summarises the current landscape of the radiopharmaceutical sciences as they pertain to oncology. In this Series paper, we describe exciting developments in radiochemistry and the production of radionuclides, the development and translation of theranostics, and the application of artificial intelligence to our field. These developments are catalysing growth in the use of radiopharmaceuticals to the benefit of patients worldwide. We also highlight some of the key issues to be addressed in the coming years to realise the full potential of radiopharmaceuticals to treat cancer. [ABSTRACT FROM AUTHOR]

Purpose: Patients with lung cancer and brain metastases represent a markedly heterogeneous population. Accurate prognosis is essential to optimally individualize care. In prior publications, we described the graded prognostic assessment (GPA), but a GPA for patients with small cell lung cancer (SCLC) has never been reported, and in non-small cell lung cancer (NSCLC), the effect of programmed death ligand 1 (PD-L1) was unknown. The 3-fold purpose of this work is to provide the initial report of an SCLC GPA, to evaluate the effect of PD-L1 on survival in patients with NSCLC, and to update the Lung GPA accordingly.Methods and Materials: A multivariable analysis of prognostic factors and treatments associated with survival was performed on 4183 patients with lung cancer (3002 adenocarcinoma, 611 nonadenocarcinoma, 570 SCLC) with newly diagnosed brain metastases between January 1, 2015, and December 31, 2020, using a multi-institutional retrospective database. Significant variables were used to update the Lung GPA.Results: Overall median survival for lung adenocarcinoma, SCLC, and nonadenocarcinoma was 17, 10, and 8 months, respectively, but varied widely by GPA from 2 to 52 months. In SCLC, the significant prognostic factors were age, performance status, extracranial metastases, and number of brain metastases. In NSCLC, the distribution of molecular markers among patients with lung adenocarcinoma and known primary tumor molecular status revealed alterations/expression in PD-L1 50% to 100%, PD-L1 1% to 49%, epidermal growth factor receptor, and anaplastic lymphoma kinase in 32%, 31%, 30%, and 7%, respectively. Median survival of patients with lung adenocarcinoma and brain metastases with 0, 1% to 49%, and ≥50% PD-L1 expression was 17, 19, and 24 months, respectively (P < .01), confirming PD-L1 is a prognostic factor. Previously identified prognostic factors for NSCLC (epidermal growth factor receptor and anaplastic lymphoma kinase status, performance status, age, number of brain metastases, and extracranial metastases) were reaffirmed. These factors were incorporated into the updated Lung GPA with robust separation between subgroups for all histologies.Conclusions: Survival for patients with lung cancer and brain metastases has improved but varies widely. The initial report of a GPA for SCLC is presented. For patients with NSCLC-adenocarcinoma and brain metastases, PD-L1 is a newly identified significant prognostic factor, and the previously identified factors were reaffirmed. The updated indices establish unique criteria for SCLC, NSCLC-nonadenocarcinoma, and NSCLC-adenocarcinoma (incorporating PD-L1). The updated Lung GPA, available for free at brainmetgpa.com, provides an accurate tool to estimate survival, individualize treatment, and stratify clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: To review the University of Iowa experience with intensity-modulated radiotherapy (IMRT) in the treatment of head-and-neck squamous cell carcinoma. Methods and Materials: From October 1999 to April 2004, 151 patients with head-and-neck squamous cell carcinoma were treated with IMRT for curative intent. One patient was lost to follow-up 2 months after treatment and therefore excluded from analysis. Of the remaining 150 patients, 99 were treated with definitive IMRT, and 51 received postoperative IMRT. Sites included were nasopharynx, 5; oropharynx, 56; larynx, 33; oral cavity, 29; hypopharynx, 8; nasal cavity/paranasal sinus, 8; and unknown primary, 11. None of the patients treated with postoperative IMRT received chemotherapy. Of 99 patients who had definitive IMRT, 68 patients received concurrent cisplatin-based chemotherapy. One patient received induction cisplatin-based chemotherapy, but no concurrent chemotherapy was given. Three clinical target volumes (CTV1, CTV2, and CTV3) were defined. The prescribed doses to CTV1, CTV2, and CTV3 in the definitive cohort were 70–74 Gy, 60 Gy, and 54 Gy, respectively. For high-risk postoperative IMRT, the prescribed doses to CTV1, CTV2, and CTV3 were 64–66 Gy, 60 Gy, and 54 Gy, respectively. For intermediate-risk postoperative IMRT, the prescribed doses to CTV1, CTV2, and CTV3 were 60 Gy, 60 Gy, and 54 Gy. Results: The median follow-up was 18 months (range, 2–60 months). All living patients were followed for at least 6 months. There were 11 local–regional failures: 7 local failures, 3 regional failures, and 1 failure both in the primary tumor and regional lymph node. There were 16 patients who failed distantly, either with distant metastasis or new lung primaries. The 2-year overall survival, local progression-free survival, locoregional progression-free survival, and distant disease-free survival rates were 85%, 94%, 92%, and 87%, respectively. The median time from treatment completion to local–regional recurrence was 4.7 months (range, 1.8 to 15.6 months). Only one marginal failure was noted in a patient who had extensive tonsil cancer with tumor extension into the orbit and cavernous sinus. Patients with oropharyngeal cancer did significantly better than patients with oral cavity and laryngeal cancer, with a 2-year local–regional control rate of 98%, compared with 78% for oral cavity cancer and 85% for laryngeal cancer (p = 0.005). There was no significant difference in local–regional control for patients who received postoperative radiation or definitive radiation (p = 0.339) and for patients who had chemotherapy or not (p = 0.402). Neither T stage nor N stage had a significant effect on local–regional control (p = 0.722 and 0.712, respectively). Conclusions: Our results have confirmed the effectiveness of IMRT in head-and-neck cancer. It offers excellent outcomes in local–regional control and overall survival. More studies are necessary to further improve the outcomes of laryngeal cancer as well as oral cavity cancer. [Copyright &y& Elsevier]

Purpose: To review our institutional experience with primary orbital lymphoma and determine the prognostic factors for survival, local control, and distant metastases. In addition, we also analyzed the risk factors for complications in the radiotherapeutic management of this tumor.Methods and Materials: Between 1973 and 1998, 47 patients (29 women [62%] and 18 men [38%], median age 69 years, range 32–89) with Stage IAE orbital lymphoma were treated with curative intent at one department. Five had bilateral orbital involvement. The tumor was located in the eyelid and extraocular muscles in 23 (44%), conjunctiva in 17 (33%), and lacrimal apparatus in 12 (23%). The histologic features according to the World Heath Organization classification of lymphoid neoplasms was follicular lymphoma in 25, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type in 8, diffuse large B-cell lymphoma in 12, mantle cell lymphoma in 6, and peripheral T-cell lymphoma in 1. For the purposes of comparison with the existing literature on orbital lymphomas, the grading system according to the Working Formulation was also recorded. The histologic grade was low in 33 (63%), intermediate in 18 (35%), and high in 1 (2%). All patients were treated with primary radiotherapy alone. The median dose for low-grade tumors was 3000 cGy (range 2000–4020); the median dose for intermediate and high-grade tumors was 4000 cGy (range 3000–5100). A lens-sparing approach was used in 19 patients (37%). Late complications for the lens and cornea were scored according to the subjective, objective, management, and analytic (SOMA) scale of the Late Effects of Normal Tissue (LENT) scoring system. The median follow-up was 55 months (range 6–232).Results: The local control rate was 100% in the 52 orbits treated. The 5-year overall survival and relapse-free survival rate was 73.6% and 65.5%, respectively. Tumor grade and location did not predict for overall survival or relapse-free survival. Seven patients (15%) developed distant recurrence (brain 2, extremity 2, mediastinum 1, liver 1, and retroperitoneum 1). One patient (2%) developed cervical node metastasis. The 5- and 10-year cataract-free survival rate was 56.7% and 32.9%, respectively. Of the 12 lens complications, 8 were LENT Grade 1 and 4 were Grade 3 toxicity. Only male gender predicted for an increased risk of cataract formation. Radiotherapy dose and technique did not predict for cataract formation; however, none of the patients who underwent the lens-sparing technique developed Grade 3 lens toxicity or required surgical correction. Of the nine corneal events, two were Grade 1, four Grade 2, and three were Grade 3 toxicity. Ten dry eyes were recorded; all were mild, and no patient had severe dry eye syndrome. Neovascular glaucoma was seen in 1 patient. No injury to the retina or optic nerve was reported.Conclusion: Radiotherapy alone is a highly effective modality in the curative management of primary orbital lymphoma. Most complications were minimal and did not require medical or surgical intervention. Although the use of the lens-sparing technique did not influence the incidence of cataractogenesis, we continue to recommend this approach whenever possible, because our experience indicates a higher grade of toxicity occurs and a higher incidence of corrective surgery is needed in patients treated without lens protection. [Copyright &y& Elsevier]

Purpose: To identify prognostic factors, define evolving patterns of care, and the effect of targeted therapies in a larger contemporary cohort of renal cell carcinoma (RCC) patients with new brain metastases (BM).Methods and Materials: A multi-institutional retrospective institutional review board-approved database of 711 RCC patients with new BM diagnosed from January 1, 2006, to December 31, 2015, was created. Clinical parameters and treatment were correlated with median survival and time from primary diagnosis to BM. Multivariable analyses were performed.Results: The median survival for the prior/present cohorts was 9.6/12 months, respectively (P < .01). Four prognostic factors (Karnofsky performance status, extracranial metastases, number of BM, and hemoglobin b) were significant for survival after the diagnosis of BM. Of the 6 drug types studied, only cytokine use after BM was associated with improved survival. The use of whole-brain radiation therapy declined from 50% to 22%, and the use of stereotactic radiosurgery alone increased from 46% to 58%. Nonneurologic causes of death were twice as common as neurologic causes.Conclusions: Additional prognostic factors refine prognostication in this larger contemporary cohort. Patterns of care have changed, and survival of RCC patients with BM has improved over time. The reasons for this improvement in survival remain unknown but may relate to more aggressive use of local brain metastasis therapy and a wider array of systemic treatment options for those patients with progressive extracranial tumor. [ABSTRACT FROM AUTHOR]

Purpose: To assess the safety of the superoxide dismutase mimetic GC4419 in combination with radiation and concurrent cisplatin for patients with oral cavity or oropharyngeal cancer (OCC) and to assess the potential of GC4419 to reduce severe oral mucositis (OM).Patients and Methods: Patients with locally advanced OCC treated with definitive or postoperative intensity modulated radiation therapy (IMRT) plus cisplatin received GC4419 by 60-minute intravenous infusion, ending <60 minutes before IMRT, Monday through Friday for 3 to 7 weeks, in a dose and duration escalation study. Oral mucositis was assessed twice weekly during and weekly after IMRT.Results: A total of 46 patients received GC4419 in 11 separate dosing and duration cohorts: dose escalation occurred in 5 cohorts receiving 15 to 112 mg/d over 3 weeks (n=20), duration escalation in 3 cohorts receiving 112 mg/d over 4 to 6 weeks (n=12), and then 3 additional cohorts receiving 30 or 90 mg/d over 6 to 7 weeks (n=14). A maximum tolerated dose was not reached. One dose-limiting toxicity (grade 3 gastroenteritis and vomiting with hyponatremia) occurred in each of 2 separate cohorts at 112 mg. Nausea/vomiting and facial paresthesia during infusion seemed to be GC4419 dose-related. Severe OM occurred through 60 Gy in 4 of 14 patients (29%) dosed for 6 to 7 weeks, with median duration of only 2.5 days.Conclusions: The safety of GC4419 concurrently with chemoradiation for OCC was acceptable. Toxicities included nausea/vomiting and paresthesia. Doses of 30 and 90 mg/d administered for 7 weeks were selected for further study. In an exploratory analysis, severe OM seemed less frequent and briefer than expected. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the present prospective clinical trial was to determine the efficacy of [(18)F]fluorothymidine (FLT)-identified active bone marrow sparing for pelvic cancer patients by correlating the FLT uptake change during and after chemoradiation therapy with hematologic toxicity.Methods and Materials: Simulation FLT positron emission tomography (PET) images were used to spare pelvic bone marrow using intensity modulated radiation therapy (IMRT BMS) for 32 patients with pelvic cancer. FLT PET scans taken during chemoradiation therapy after 1 and 2 weeks and 30 days and 1 year after completion of chemoradiation therapy were used to evaluate the acute and chronic dose response of pelvic bone marrow. Complete blood counts were recorded at each imaging point to correlate the FLT uptake change with systemic hematologic toxicity.Results: IMRT BMS plans significantly reduced the dose to the pelvic regions identified with FLT uptake compared with control IMRT plans (P<.001, paired t test). Radiation doses of 4 Gy caused an ∼50% decrease in FLT uptake in the pelvic bone marrow after either 1 or 2 weeks of chemoradiation therapy. Additionally, subjects with more FLT-identified bone marrow exposed to ≥4 Gy after 1 week developed grade 2 leukopenia sooner than subjects with less marrow exposed to ≥4 Gy (P<.05, Cox regression analysis). Apparent bone marrow recovery at 30 days after therapy was not maintained 1 year after chemotherapy. The FLT uptake in the pelvic bone marrow regions that received >35 Gy was 18.8% ± 1.8% greater at 30 days after therapy than at 1 year after therapy. The white blood cell, platelet, lymphocyte, and neutrophil counts at 1 year after therapy were all lower than the pretherapy levels (P<.05, paired t test).Conclusions: IMRT BMS plans reduced the dose to FLT-identified pelvic bone marrow for pelvic cancer patients. However, reducing hematologic toxicity is challenging owing to the acute radiation sensitivity (∼4 Gy) and chronic suppression of activity in bone marrow receiving radiation doses >35 Gy, as measured by the FLT uptake change correlated with the complete blood cell counts. [ABSTRACT FROM AUTHOR]

Purpose To evaluate dynamic [ 18 F]-fluorodeoxyglucose (FDG) uptake methodology as a post–radiation therapy (RT) response assessment tool, potentially enabling accurate tumor and therapy-related inflammation differentiation, improving the posttherapy value of FDG–positron emission tomography/computed tomography (FDG-PET/CT). Methods and Materials We prospectively enrolled head-and-neck squamous cell carcinoma patients who completed RT, with scheduled 3-month post-RT FDG-PET/CT. Patients underwent our standard whole-body PET/CT scan at 90 minutes, with the addition of head-and-neck PET/CT scans at 60 and 120 minutes. Maximum standardized uptake values (SUV max ) of regions of interest were measured at 60, 90, and 120 minutes. The SUV max slope between 60 and 120 minutes and change of SUV max slope before and after 90 minutes were calculated. Data were analyzed by primary site and nodal site disease status using the Cox regression model and Wilcoxon rank sum test. Outcomes were based on pathologic and clinical follow-up. Results A total of 84 patients were enrolled, with 79 primary and 43 nodal evaluable sites. Twenty-eight sites were interpreted as positive or equivocal (18 primary, 8 nodal, 2 distant) on 3-month 90-minute FDG-PET/CT. Median follow-up was 13.3 months. All measured SUV endpoints predicted recurrence. Change of SUV max slope after 90 minutes more accurately identified nonrecurrence in positive or equivocal sites than our current standard of SUV max ≥2.5 ( P =.02). Conclusions The positive predictive value of post-RT FDG-PET/CT may significantly improve using novel second derivative analysis of dynamic triphasic FDG-PET/CT SUV max slope, accurately distinguishing tumor from inflammation on positive and equivocal scans. [ABSTRACT FROM AUTHOR]

Objective: Chordomas carry significant morbidity due to their growth patterns and surgical constraints in resection. En bloc resection, when feasible, is the ideal treatment goal, but is associated with significant morbidity. We sought to elucidate the relationship between extent of surgery, location and radiotherapy in relation to overall disease and progression free survival (PFS). Methods: We reviewed case records for all patients with a primary histopathological diagnosis of clival and spinal chordomas that was presented to our institution between 1978 and 2010. Results: A total of 49 patients (location: n = 30, skull base/clival; n = 12 vertebral column; n = 7 sacrum) were identified with mean follow-up period of 6.3 years (range 0.25 months-33 years). Improved 5 year and 10 year survival rates were noted following gross total resection (n = 8, 5 year and 10 year survival = 88%) as compared to patients that underwent subtotal resection (n = 41, 55% and 31%, respectively), (p-value > 0.05, GTR versus STR). Adjuvant high-dose stereotactic fractionated radiotherapy (HS-FSRT) significantly improved 5 year PFS in craniocervical chordoma patients (70%, n = 13) as compared to standard dose radiation therapy (20%, n = 16; p-value = 0.03). Overall 10 year survival for craniocervical patients undergoing HD-FSRT (40%) was however not significantly different in comparison with conventional radiotherapy (45%). Sacral chordomas had the worst prognosis with 3 year survival of 28.6%. Conclusions: GTR offers the best prognosis for improved long-term survival. Adjuvant HD FSRT for craniocervical/ clival chordomas significantly improves disease free survival though the long-term benefits on survival have yet to be established. Sacral chordomas are associated with a worse prognosis and poor long-term survival. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the utility of 3-dimensional magnetic resonance (3D-MR) proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme. Methods and Materials Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium-enhanced MR images at simulation and at boost treatment planning after 17 to 20 fractions of radiation therapy. All patients received standard radiation therapy (RT) with concurrent temozolomide followed by adjuvant temozolomide. Imaging for response assessment consisted of MR scans every 2 months. Progression-free survival was defined by the criteria of MacDonald et al. MRSI images obtained at initial simulation were analyzed for choline/N-acetylaspartate ratios (Cho/NAA) on a voxel-by-voxel basis with abnormal activity defined as Cho/NAA ≥2. These images were compared on anatomically matched MRSI data collected after 3 weeks of RT. Changes in Cho/NAA between pretherapy and third-week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression-free survival, radiation dose and location of recurrence using Cox proportional hazards regression. Results After a median follow-up time of 8.6 months, 50% of patients had experienced progression based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (P<.01). Patients with an increase in mean or median Cho/NAA values at the third-week RT scan had a significantly greater chance of early progression (P<.01). An increased Cho/NAA at the third-week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval, 1.10-6.71; P=.03). Most patients received the prescription dose of RT to the Cho/NAA ≥2 volume, where recurrence most often occurred. Conclusion Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of early progression. The potential impact for risk-adaptive therapy based on early spectroscopic findings is suggested. [ABSTRACT FROM AUTHOR]

Abstract: To develop an optimal field-splitting algorithm of minimal complexity and verify the algorithm using head-and-neck (H&N) and female pelvic intensity-modulated radiotherapy (IMRT) cases. An optimal field-splitting algorithm was developed in which a large intensity map (IM) was split into multiple sub-IMs (≥2). The algorithm reduced the total complexity by minimizing the monitor units (MU) delivered and segment number of each sub-IM. The algorithm was verified through comparison studies with the algorithm as used in a commercial treatment planning system. Seven IMRT, H&N, and female pelvic cancer cases (54 IMs) were analyzed by MU, segment numbers, and dose distributions. The optimal field-splitting algorithm was found to reduce both total MU and the total number of segments. We found on average a 7.9 ± 11.8% and 9.6 ± 18.2% reduction in MU and segment numbers for H&N IMRT cases with an 11.9 ± 17.4% and 11.1 ± 13.7% reduction for female pelvic cases. The overall percent (absolute) reduction in the numbers of MU and segments were found to be on average −9.7 ± 14.6% (−15 ± 25 MU) and −10.3 ± 16.3% (−3 ± 5), respectively. In addition, all dose distributions from the optimal field-splitting method showed improved dose distributions. The optimal field-splitting algorithm shows considerable improvements in both total MU and total segment number. The algorithm is expected to be beneficial for the radiotherapy treatment of large-field IMRT. [Copyright &y& Elsevier]

Abstract: Quantitative imaging using computed tomography, magnetic resonance imaging and positron emission tomography modalities will play an increasingly important role in the design of oncology trials addressing molecularly targeted, personalized therapies. The advent of molecularly targeted therapies, exemplified by antiangiogenic drugs, creates new complexities in the assessment of response. The Quantitative Imaging Network addresses the need for imaging modalities which can accurately and reproducibly measure not just change in tumor size but changes in relevant metabolic parameters, modulation of relevant signaling pathways, drug delivery to tumor and differentiation of apoptotic cell death from other changes in tumor volume. This article provides an overview of the applications of quantitative imaging to phase 0 through phase 3 oncology trials. We describe the use of a range of quantitative imaging modalities in specific tumor types including malignant gliomas, lung cancer, head and neck cancer, lymphoma, breast cancer, prostate cancer and sarcoma. In the concluding section, we discuss potential constraints on clinical trials using quantitative imaging, including complexity of trial conduct, impact on subject recruitment, incremental costs and institutional barriers. Strategies for overcoming these constraints are presented. [Copyright &y& Elsevier]

Abstract: Background: Response evaluation criteria in solid tumors (RECIST) is the accepted method for determining tumor progression. However, RECIST may not estimate disease burden accurately because the axial plane often does not produce the actual longest diameter. Volumetric measurements may be an alternative to better determine tumor size. Our aim was to compare volumetric measurements with RECIST in pancreatic ductal adenocarcinomas (PDA) and hepatocellular carcinomas (HCC). Methods: RECIST and volumetric measurements were determined in 9 patients with metastatic PDA and 17 patients with HCC who subsequently underwent liver transplantation. Gross pathologic measurements after hepatectomy also were analyzed for volumes. Results: Three-dimensional diameter in volumetric analysis was 38% and 36% higher than RECIST diameter in PDA and HCC, respectively (P < .01). However, RECIST yielded 78% and 23% larger estimated tumor volumes than volumetric analysis in PDA and HCC, respectively (P < .01). Gross pathologic volume in HCC showed a linear correlation with both volumetric analysis (r = .95; P < .01) and RECIST (r = .96; P < .01) but RECIST significantly overestimated gross pathologic volume by an average of 28% (P < .01) whereas volumetric analysis was similar to gross pathologic volume (P = .56). In categorizing treatment response in PDA, RECIST and volumetric analysis were in moderate agreement (κ = .49). Conclusions: RECIST significantly may overestimate tumor burden compared with volumetric measurements in both PDA and HCC. Volumetric analysis may be the preferred method to detect tumor progression. [Copyright &y& Elsevier]

Purpose: To determine the pattern and risk factors for distant metastases in head-and-neck squamous cell carcinoma (HNSCC) after curative treatment with intensity-modulated radiotherapy (IMRT). Methods and Materials: This was a retrospective study of 284 HNSCC patients treated in a single institution with IMRT. Sites included were oropharynx (125), oral cavity (70), larynx (55), hypopharynx (17), and unknown primary (17). American Joint Committee on Cancer stage distribution includes I (3), II (19), III (42), and IV (203). There were 224 males and 60 females with a median age of 57. One hundred eighty-six patients were treated with definitive IMRT and 98 postoperative IMRT. One hundred forty-nine patients also received concurrent cisplatin-based chemotherapy. Results: The median follow-up for all patients was 22.8 months (range, 0.07–77.3 months) and 29.5 months (4.23–77.3 months) for living patients. The 3-year local recurrence-free survival, regional recurrence-free survival, locoregional recurrence-free survival, distant metastasis-free survival, and overall survival were 94.6%, 96.4%, 92.5%, 84.1%, and 68.95%, respectively. There were 45 patients with distant metastasis. In multivariate analysis, distant metastasis was strongly associated with N stage (p = 0.046), T stage (p < 0.0001), and pretreatment maximum standardized uptake value of the lymph node (p = 0.006), but not associated with age, gender, disease sites, pretreatment standardized uptake value of the primary tumor, or locoregional control. The freedom from distant metastasis at 3 years was 98.1% for no factors, 88.6% for one factor, 68.3% for two factors, and 41.7% for three factors (p < 0.0001 by log–rank test). Conclusion: With advanced radiation techniques and concurrent chemotherapy, the failure pattern has changed with more patients failing distantly. The majority of patients with distant metastases had no local or regional failures, indicating that these patients might have microscopic distant disease before treatment. The clinical factors identified here should be incorporated in future clinical trials. [Copyright &y& Elsevier]

Abstract: Introduction: The kinetics of the bone marrow uptake of 3′-deoxy-3′-[18F]fluorothymidine (FLT) before and early after initiation of chemoradiation therapy was investigated in patients with head and neck cancer. Methods: Fourteen subjects with head and neck cancer underwent FLT positron emission tomography (PET) at baseline and after 10 Gy of radiation therapy. Thirteen subjects also received one cycle of platinum-based chemotherapy before the second FLT PET. Kinetic parameters, including the flux constant based on compartmental analysis (K FLT) and the Patlak constant (K Patlak) for cervical marrow, were calculated. Standardized uptake values (SUVs) for the cervical marrow (inside the radiation field) and lumbar spine marrow (outside the radiation field) were also determined. Results: There was a significant drop in FLT uptake in the bone marrow inside the radiation field. Mean pretreatment uptake values for the cervical spine were SUV=3.08±0.66, K FLT=0.045±0.016 min−1 and K Patlak=0.039±0.013 min−1. After treatment, these values were SUV=0.74±0.19, K FLT=0.011±0.005 min−1 and K Patlak=0.005±0.002 min−1. Compartmental analysis revealed a significant drop in k 3 in irradiated cervical marrow. FLT uptake in the bone marrow outside the radiation field exhibited a significantly smaller decrease. Conclusions: There is a marked decrease in FLT uptake in irradiated bone marrow after 10 Gy of radiation therapy to the head and neck. The drop in FLT uptake in irradiated marrow is due to a significant decrease in the net phosphorylation rate of FLT. [Copyright &y& Elsevier]

Purpose: Human papilloma virus (HPV)-associated cancers of the head and neck (H&N) are increasing in frequency and are often treated with radiation. There are conflicting data in the literature regarding the radiation response in the presence of HPV infection, with some data suggesting they may be more sensitive to radiation. There are few studies looking at in vitro effects of HPV and further sensitization by inhibitors of specific signaling pathways. We are in the process of starting a clinical trial in H&N cancer patients using nelfinavir (NFV) (which inhibits Akt) and it would be important to know the effect of HPV on radiation response ± NFV. Methods and Materials: Two naturally infected HPV-16 cell lines (UPCI-SCC90 and UMSCC47) and the HPV-negative SQ20B H&N squamous carcinoma cells were used. Western blots with or without 10 uM NFV were done to evaluate signaling from the PI3K-Akt pathway. Clonogenic assays were done in the three cell lines with or without NFV. Results: Both UPCI-SCC90 and UMSCC47 cells were sensitive to radiation as compared with SQ20B and the degree corresponded to Akt activation. The SQ20B cell line has an activating mutation in EGFR resulting in phosphorylation (P) of Akt; UMSCC47 has decreased P-phosphatase and TENsin (PTEN), resulting in increased P-Akt; UPCI-SCC90 had overexpression of P-PTEN and decreased P-Akt. NFV resulted in downregulation of Akt in all three cell lines, resulting in sensitization to radiation. Conclusions: HPV-infected H&N cancers are sensitive to radiation. The degree of sensitivity correlates to Akt activation and they can be further sensitized by NFV. [Copyright &y& Elsevier]

Purpose: To determine the accuracy and prognostic significance of post-treatment [(18)F]-fluorodeoxyglucose positron emission tomography (FDG-PET) in head-and-neck squamous cell carcinoma after radiotherapy (RT). Methods and Materials: This was a retrospective study of 188 patients with head-and-neck squamous cell carcinoma who had undergone FDG-PET within 12 months after completing RT. All living patients had >/=1 year of follow-up after FDG-PET. All patients had undergone intensity-modulated RT, 128 with definitive and 60 with postoperative intensity-modulated RT. Results: For all patients, the median follow-up after RT completion was 32.6 months and after FDG-PET was 29.2 months. For the neck, 171 patients had negative FDG-PET findings. Of these results, two were falsely negative. Seventeen patients had positive FDG-PET findings, of which 12 were true-positive findings. The sensitivity, specificity, positive predictive value, and negative predictive value for FDG-PET in the assessment of the treatment response in the neck was 86%, 97%, 71%, and 99%, respectively. For the primary site, 151 patients had negative FDG-PET findings, of which two were falsely negative. Thirty-seven patients had positive FDG-PET findings, of which 12 were true-positive findings. The sensitivity, specificity, positive predictive value, and negative predictive value for FDG-PET in the assessment of the treatment response in the primary site was 86%, 86%, 32.4%, and 98.7%, respectively. Patients with positive post-RT PET findings had significantly worse 3-year overall survival and disease-free survival. Conclusion: The results of our study have shown that the findings of post-RT FDG-PET have a high negative predictive value and are a significant prognostic factor. It can provide guidance for the management of head-and-neck cancer after definitive treatment. [ABSTRACT FROM AUTHOR]

Purpose: To determine the accuracy and prognostic significance of post-treatment [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) in head-and-neck squamous cell carcinoma after radiotherapy (RT). Methods and Materials: This was a retrospective study of 188 patients with head-and-neck squamous cell carcinoma who had undergone FDG-PET within 12 months after completing RT. All living patients had ≥1 year of follow-up after FDG-PET. All patients had undergone intensity-modulated RT, 128 with definitive and 60 with postoperative intensity-modulated RT. Results: For all patients, the median follow-up after RT completion was 32.6 months and after FDG-PET was 29.2 months. For the neck, 171 patients had negative FDG-PET findings. Of these results, two were falsely negative. Seventeen patients had positive FDG-PET findings, of which 12 were true-positive findings. The sensitivity, specificity, positive predictive value, and negative predictive value for FDG-PET in the assessment of the treatment response in the neck was 86%, 97%, 71%, and 99%, respectively. For the primary site, 151 patients had negative FDG-PET findings, of which two were falsely negative. Thirty-seven patients had positive FDG-PET findings, of which 12 were true-positive findings. The sensitivity, specificity, positive predictive value, and negative predictive value for FDG-PET in the assessment of the treatment response in the primary site was 86%, 86%, 32.4%, and 98.7%, respectively. Patients with positive post-RT PET findings had significantly worse 3-year overall survival and disease-free survival. Conclusion: The results of our study have shown that the findings of post-RT FDG-PET have a high negative predictive value and are a significant prognostic factor. It can provide guidance for the management of head-and-neck cancer after definitive treatment. [Copyright &y& Elsevier]

Purpose: Determine the degree of interfraction prostate motion and its components measured by using daily megavoltage (MV) cone beam computed tomography (CBCT) imaging. Methods and Materials: A total of 984 daily MV CBCT images from 24 patients undergoing definitive intensity-modulated radiotherapy for localized prostate cancer were analyzed retrospectively. Pretreatment couch shifts, based on physician registration of MV CBCT to planning CT data sets, were used as a measure of daily interfraction motion. Off-line bony registration was performed to separate bony misalignment from internal organ motion. Interobserver and intraobserver variation studies were performed on 20 MV CBCT images. Results: Mean interfraction prostate motion was 6.7 mm, with the greatest single-axis deviation in the anterior-posterior (AP) direction. The largest positional inaccuracy was accounted for by systematic deviations in bony misalignment, whereas random deviations occurred from bony misalignment and internal prostate motion. In the aggregate, AP motion did not correlate with days elapsed since beginning therapy or on average with rectal size at treatment planning. Interobserver variation was greatest in the AP direction, decreased in experienced observers, and further decreased in intraobserver studies. Mean interfraction motion during the first 6 days of therapy, when used as a subsequent offset, reduced acceptable AP planning target volume margins by 50%. Conclusion: The MV CBCT is a practical direct method of daily localization that shows significant interfraction motion with respect to conventional three-dimensional conformal and intensity-modulated radiotherapy margins, similar to that measured in other modalities. [Copyright &y& Elsevier]

Purpose: To compare health-related quality-of-life (HRQOL) outcomes of patients with oropharyngeal squamous cell carcinoma treated using intensity-modulated radiotherapy (IMRT) vs. conventional radiotherapy (CRT). Patients and Methods: Patients with oropharyngeal squamous cell carcinoma were extracted from the database of an ongoing longitudinal Outcome Assessment Project. Eligible criteria included (1) treated with definitive radiation, and (2) provided 12-month posttreatment HRQOL data. Excluded were 7 patients who received IMRT before October 1, 2002, during this institution''s developmental phase of the IMRT technique. The HRQOL outcomes of patients treated with IMRT were compared with those of patients who received CRT. Results: Twenty-six patients treated using IMRT and 27 patients treated using CRT were included. Patients in the IMRT group were older and had more advanced-stage diseases and more patients received concurrent chemotherapy. However, the IMRT group had higher mean Head and Neck Cancer Inventory scores (which represent better outcomes) for each of the four head-and-neck cancer–specific domains, including eating, speech, aesthetics, and social disruption, at 12 months after treatment. A significantly greater percentage of patients in the CRT group had restricted diets compared with those in the IMRT group (48.0% vs. 16.0%, p = 0.032). At 3 months after treatment, both groups had significant decreases from pretreatment eating scores. However, the IMRT group had a significant improvement during the first year, but the CRT group had only small improvement. Conclusions: Proper delivery of IMRT can improve HRQOL for patients with oropharyngeal cancer compared with CRT. [Copyright &y& Elsevier]

Purpose: To determine whether the response of human head and neck cancer xenografts to cisplatin (CIS) could be enhanced with 2-deoxy-D-glucose (2DG); whether 2-[(18)F]-fluoro-2-deoxy-D-glucose (FDG) uptake correlated with responses to this drug combination; and whether 2DG would enhance CIS-induced radiosensitization.Methods and Materials: Clonogenic survival responses to CIS + 2DG were determined in FaDu and Cal-27 cells and reduced/oxidized glutathione levels were monitored as parameters indicative of oxidative stress. The efficacy of CIS + 2DG was determined in FaDu and Cal-27 xenografts, and FDG uptake was determined by using positron emission tomography.Results: Use of CIS + 2DG enhanced cell killing of FaDu and Cal-27 cells compared with either drug alone while increasing the percentage of oxidized glutathione in vitro. Use of CIS + 2DG inhibited FaDu and Cal-27 tumor growth and increased disease-free survival compared with either drug alone. The Cal-27 tumors showed greater pretreatment FDG uptake and increased disease-free survival when treated with 2DG + CIS relative to FaDu tumors. Treatment with 2DG enhanced CIS-induced radiosensitization in FaDu tumor cells grown in vitro and in vivo and resulted in apparent cures in 50% of tumors.Conclusions: These results show the enhanced therapeutic efficacy of CIS + 2DG in human head and neck cancer cells in vitro and in vivo compared with either drug alone, as well as the potential for FDG uptake to predict tumor sensitivity to 2DG + CIS. These findings provide a strong rationale for evaluating 2DG + CIS in combined-modality head and neck cancer therapy with radiation in a clinical setting. [ABSTRACT FROM AUTHOR]

Purpose: To test the hypothesis that radiation dose to key sites in the upper aerodigestive tract is associated with long-term functional outcome after (chemo)radiotherapy for head-and-neck cancers. Methods and Materials: This study examined the outcome for 27 patients treated with intensity-modulated radiotherapy for definitive management of their head-and-neck cancer who were disease free for at least 1 year after treatment. Head-and-neck cancer-specific quality of life (QoL) was assessed before treatment and at 1 year after treatment. Type of diet tolerated, presence of a feeding tube, and degree of weight loss 1 year after treatment were also used as outcome measures. Radiation doses delivered to various points along the upper aerodigestive tract, including base of tongue, lateral pharyngeal walls, and laryngeal structures, were determined from each treatment plan. Radiation doses for each of these points were tested for correlation with outcome measures. Results: Higher doses delivered to the aryepiglottic folds, false vocal cords, and lateral pharyngeal walls near the false cords correlated with a more restrictive diet, and higher doses to the aryepiglottic folds correlated with greater weight loss (p < 0.05) 1 year after therapy. Better posttreatment speech QoL scores were associated with lower doses delivered to structures within and surrounding the larynx. Conclusion: Our data show an inverse relationship between radiation dose delivered to laryngeal structures and speech and diet and QoL outcomes after definitive (chemo)radiation treatment. These findings suggest that efforts to deliver lower doses to laryngeal structures may improve outcomes after definitive (chemo)radiation therapy. [Copyright &y& Elsevier]

Purpose: The objective of this study was to determine regional control of local regional advanced head and neck squamous cell carcinoma (HNSCC) treated with intensity-modulated radiotherapy (IMRT), along with the role and selection criteria for neck dissection after IMRT. Methods and Materials: A total of 90 patients with stage N2A or greater HNSCC were treated with definitive IMRT from December 1999 to July 2005. Three clinical target volumes were defined and were treated to 70 to 74 Gy, 60 Gy, and 54 Gy, respectively. Neck dissection was performed for selected patients after IMRT. Selection criteria evolved during this period with emphasis on post-IMRT [18F] fluorodeoxyglucose positron emission tomography in recent years. Results: Median follow-up for all patients was 29 months (range, 0.2–74 months). All living patients were followed at least 9 months after completing treatment. Thirteen patients underwent neck dissection after IMRT because of residual lymphadenopathy. Of these, 6 contained residual viable tumor. Three patients with persistent adenopathy did not undergo neck dissection: 2 refused and 1 had lung metastasis. Among the remaining 74 patients who were observed without neck dissection, there was only 1 case of regional failure. Among all 90 patients in this study, the 3-year local and regional control was 96.3% and 95.4%, respectively. Conclusions: Appropriately delivered IMRT has excellent dose coverage for cervical lymph nodes. A high radiation dose can be safely delivered to the abnormal lymph nodes. There is a high complete response rate. Routine planned neck dissection for patients with N2A and higher stage after IMRT is not necessary. Post-IMRT [18F] fluorodeoxyglucose positron emission tomography is a useful tool in selecting patients appropriate for neck dissection. [Copyright &y& Elsevier]

Abstract: Stereotactic radiosurgery and image-guided radiotherapy (IGRT) place enhanced demands on treatment delivery machines. In this study, we describe a high-dose-rate output accelerator as a part of our stereotactic IGRT delivery system. The linac is a Siemens Oncor without a flattening filter, and enables dose rates to reach 1000 monitor units (MUs) per minute. Even at this high-dose-rate, the linac dosimetry system remains robust; constancy, linearity, and beam energy remain within 1% for 3 to 1000 MU. Dose profiles for larger field sizes are not flat, but they are radially symmetric and, as such, able to be modeled by a treatment planning system. Target localization is performed via optical guidance utilizing a 3-dimensional (3D) ultrasound probe coupled to an array of 4 infrared light-emitting diodes. These diodes are identified by a fixed infrared camera system that determines diode position and, by extension, all objects imaged in the room coordinate system. This system provides sub-millimeter localization accuracy for cranial applications and better than 1.5 mm for extracranial applications. Because stereotactic IGRT can require significantly longer times for treatment delivery, the advantages of the high-dose-rate design and its direct impact on IGRT are discussed. [Copyright &y& Elsevier]

Purpose: Determine the failure patterns of oral cavity squamous cell carcinoma (SCC) treated with intensity-modulated radiotherapy (IMRT). Methods and Materials: Between May 2001 and July 2005, 55 patients with oral cavity SCC were treated with IMRT for curative intent. Forty-nine received postoperative IMRT, 5 definitive IMRT, and 1 neoadjuvant. Three target volumes were defined (clinical target CTV1, CTV2, and CTV3). The failure patterns were determined by coregistration or comparison of the treatment planning computed tomography to the images obtained at the time of recurrence. Results: The median follow-up for all patients was 17.1 months (range, 0.27-59.3 months). The median follow-up for living patients was 23.9 months (range, 9.3-59.3 months). Nine patients had locoregional failures: 4 local failures only, 2 regional failures only, and 3 had both local and regional failures. Five patients failed distantly; of these, 3 also had locoregional failures. The 2-year overall survival, disease-specific survival, local recurrence-free survival, locoregional recurrence-free survival, and distant disease-free survival was 68%, 74%, 85%, 82%, and 89%, respectively. The median time from treatment completion to locoregional recurrence was 4.1 months (range, 3.0-12.1 months). Except for 1 patient who failed in contralateral lower neck outside the radiation field, all failed in areas that had received a high dose of radiation. The locoregional control is strongly correlated with extracapsular extension. Conclusions: Intensity-modulated RT is effective for oral cavity SCC. Most failures are in-field failures. Further clinical studies are necessary to improve the outcomes of patients with high-risk features, particularly for those with extracapsular extension. [ABSTRACT FROM AUTHOR]

Purpose: The role of neck dissection after definitive radiation for head-and-neck cancer is controversial. We select patients for neck dissection based on postradiation therapy (post-RT), computed tomography (CT), and [18F] fluorodeoxyglucose positron emission tomography (FDG PET). We summarize the clinical outcomes of patients treated with this policy to further elucidate the role of FDG PET in decision making for neck dissection after primary radiotherapy. Methods and Materials: Between December 1999 and February 2004, 53 eligible patients were identified. These patients had stage N2A or higher head-and-neck squamous cell carcinoma and had complete response of the primary tumor after definitive radiation with or without chemotherapy. PET or computed tomography (CT) scans were performed within 6 months after treatment. Neck dissection was performed in patients with residual lymphadenopathy (identified by clinical examination or CT) and a positive PET scan. Those without residual lymph nodes and a negative PET were observed without neck dissection. For patients with residual lymphadenopathy, but a negative PET scan, neck dissection was performed at the discretion of the attending surgeon and decision of the patient. There was a total of 70 heminecks available for analysis (17 patients had bilateral neck disease). Results: There were 21 heminecks with residual lymphadenopathy identified on CT imaging or clinical examination and negative PET. Of these, 4 had neck dissection and were pathologically negative. The remaining 17 were observed without neck dissection. There was a total of 42 heminecks without residual lymph nodes on post-RT CT imaging or clinical examination with a negative PET. They were also observed without neck dissection. Seven heminecks had a positive PET scan and residual lymphadenopathy. Six of them had neck dissection and 1 had fine-needle aspiration of a residual node; 3 contained residual viable cancer and 4 were pathologically negative. At median follow up of 26 months (range, 12-57 months), no regional failure was identified. The negative predictive value of PET was 100% and positive predictive value was 43%. Conclusion: For patients who have no evidence of residual lymphadenopathy and a negative FDG PET scan 12 weeks after definitive radiation, neck dissection can be safely withheld. Even in cases in which small residual lymphadenopathy was observed, regional recurrences have not occurred when the post-RT PET scan was negative and neck dissection was withheld. For patients with large residual lymphadenopathy (greater than 2.0-3.0 cm in size) but a negative post-RT FDG PET, further studies with longer follow-up are necessary to determine the appropriateness of withholding neck dissection. [ABSTRACT FROM AUTHOR]

Purpose: To review the initial clinical experience with frameless stereotactic radiosurgery (SRS) for treating intracranial metastatic disease. Methods and Materials: Sixty-four patients received frameless SRS for intracranial metastatic disease. Minimum follow-up was 6 months with none lost to follow-up. Patients had a median of 2 metastases and a maximum of 4. The median number of isocenters was 2 with median arcs of 10 and median dose of 17.5 Gy. Thirteen patients were treated for progressive/recurrent disease after surgical resection or whole brain radiotherapy (WBRT). Fifty-one patients were treated with frameless SRS as an an adjunct to initial treatment. Of the total treated, 17 were treated with SRS alone, 20 were treated with WBRT plus SRS, 16 were treated with surgical resection plus SRS, and the remaining 11 were treated with surgical resection plus WBRT plus SRS. Results: With a median actuarial follow-up period of 8.2 months, ultimate local control was 88%. The median time to progression was 8.1 months. The median overall survival was 8.7 months. Of the 17 patients treated with SRS alone, 86% had ultimate local control with mean overall survival of 7.1 months. Of the 13 patients who received surgical resection plus SRS without WBRT as primary treatment, there was 85% ultimate local control with an overall survival of 10.3 months. Three patients treated with initial surgery alone had recurrence treated with SRS 2–3 months after resection. All these patients obtained local control and median survival was >10 months. Of the 13 patients who received WBRT followed by SRS as boost treatment, 92% had local control and mean overall survival was 7.3 months. Of 7 patients who received SRS after recurrence after WBRT, 100% had local control with median survival of 8.2 months. For 8 patients who received surgery followed by WBRT and SRS, local control was 50%; however, ultimate intracranial control was achieved in 7 of 8 patients with repeat SRS and surgical resection. The overall survival in this group of patients was 14.7 months. No patient had a serious (Grade 3 or higher) complication requiring intervention. Conclusions: Frameless optically guided radiosurgery is less invasive, can be performed as a standard radiotherapy-based simulation procedure, and maintains submillimetric accuracy. Our initial results with frameless SRS for metastatic disease suggest survival times and local control (88%) eqiuvalent to frame-based methodologies. Practical noninvasive delivery makes treatment and potential retreatment to avoid WBRT more feasible. [Copyright &y& Elsevier]

Purpose: [(18)F] fluorodeoxyglucose positron emission tomography (FDG PET) imaging has been shown to be valuable in early detection of persistent and recurrent head-and-neck cancer after treatment. Previous studies have reported its use in patients treated with conventional radiation. Many patients are now treated with intensity-modulated radiation treatment (IMRT). We evaluated the value of FDG PET in the assessment of treatment response and surveillance in head-and-neck cancer patients treated with IMRT. Methods and Materials: We performed a retrospective review of 85 head-and-neck cancer patients treated with IMRT at our institution between December 2000 and September 2003 who had FDG PET in their follow-up. Of these, 58 were treated with primary IMRT with or without chemotherapy, and 27 were treated with postoperative IMRT. Results: Sixty-four patients had negative initial FDG PET after treatment. Forty of them, who had 6 to 24 months of follow-up after the imaging study, had no evidence of local or regional recurrence, although three of them developed distant disease. Twenty-one patients had a positive initial FDG PET after treatment, with 11 positive at the primary site, 9 positive in the neck, and 3 positive distantly. Six of 11 patients with a positive FDG PET at the primary site were true positive, and 3 had salvage surgery. Eight of 9 patients positive in the neck had a salvage neck dissection. One had fine needle aspiration of the lymph node with positive cytology but refused surgery later. For patients with follow-up of 6 months and longer, only 1 of 45 patients with a negative initial FDG PET at the primary site developed a local recurrence. None of 49 patients with a negative initial FDG PET in the neck developed a regional recurrence. Two cases are presented in which abnormal FDG PET preceded laryngoscopy or computed tomography in detection of tumor recurrences. Conclusions: FDG PET is useful in the posttreatment management of head-and-neck cancer patients treated with IMRT. It is highly accurate in the detection of persistent and recurrent disease after treatment and allows salvage treatment to be initiated in a timely manner. It also provides prognostic information concerning the risk of recurrence after curative therapy. [ABSTRACT FROM AUTHOR]

Purpose: The role of neck dissection after radiation therapy ([RT] with or without chemotherapy) for regionally advanced head and neck cancer is controversial. As much as 50% of residual lymphadenopathy after radiation has no viable tumor cells present on histopathologic analysis. [18F] fluorodeoxyglucose positron emission tomography (FDG PET) imaging can detect metabolically active cancer. This study examines the ability of post–RT FDG PET imaging to predict the tumor status of residual lymphadenopathy after nonsurgical management of regionally advanced neck disease.Methods and material: From February 2000 to October 2002, 41 patients were treated definitively by radiation (with or without chemotherapy) and underwent FDG PET and computed tomography (CT) imaging after treatment to assess response. Patients with negative CT and FDG PET scans were observed and did not undergo neck dissection. Patients with radiographically persistent lymphadenopathy underwent either neck dissection or fine-needle aspiration of the lymph nodes using ultrasound guidance. The results of the FDG PET scans were correlated with the pathologic findings.Results: Twelve patients with persistent lymphadenopathy underwent either neck dissection or fine-needle aspiration. Four of the 12 were found to have viable residual tumor in the cervical lymph nodes. The pathology did not correlate with the size of the lymph nodes in the pre–RT or post–RT CT studies. However, the pathology correlated strongly with the post–RT FDG PET studies. All patients with a negative post–RT FDG PET or those with a maximum standardized uptake value (SUVmax) of less than 3.0 in the post–RT FDG PET were found to be free of residual viable tumor. Using an SUVmax of less than 3.0 as the criterion for a negative FDG PET study, the negative predictive value was 100% and the positive predictive value was 80%.Conclusions: A negative post–RT FDG PET scan is very predictive of negative pathology in neck dissection or fine-needle aspiration even with large residual lymphadenopathy. Therefore, if the post–RT FDG PET scan is negative, neck dissection might not be required for regional control. A prospective study with longer follow-up and greater patient numbers is needed to determine whether a policy of deferring neck dissection based on a negative FDG PET is supported. [Copyright &y& Elsevier]

: PurposeA simple and robust index for ranking rival stereotactic radiosurgery plans is presented.: MethodsThe radiosurgery plan score index, CGI (Conformity/Gradient Index), is an average of a conformity score and a gradient score. Computation of the CGI score is simple, requiring only three pieces of data: (1) the total volume irradiated to the prescription isodose level, (2) the volume of the target, and (3) the total volume irradiated at half of the prescription isodose level. The overall CGI Index is a simple function of these three pieces of data.: ResultsWhen multiple sets of rival stereotactic radiosurgery plans were ranked with respect to this single score index, the resulting plan rankings closely matched the plan rankings according to biologic indices (calculated nontarget brain normal tissue complication probabilities).: ConclusionsThe CGI is a simple and fast plan evaluation tool that can assist the radiosurgery planner in evaluating and optimizing multiple candidate radiosurgery plans. [Copyright &y& Elsevier]

: PurposeIntensity-modulated radiotherapy (IMRT) has been shown to reduce the radiation dose to small bowel in pelvic RT in gynecology patients. Prone positioning has also been used to decrease small bowel dose by displacement of small bowel from the RT field in these patients. The purpose of this study was to determine whether the combination of both IMRT and prone positioning on a belly board can reduce small bowel dose further in gynecologic cancer patients undergoing pelvic RT.: Methods and materialsIMRT plans for pelvic RT were computed in 16 patients with gynecologic cancer who had undergone planning CT scans in both the supine and the prone positions on a belly board. For the gross tumor volume, the uterus, cervix, and tumor (or postoperative region) were traced. The clinical target volume was defined as the vessels and lymph nodes from the obturator level to the aortic bifurcation, presacral region, and upper 4 cm of the vagina, in addition to gross tumor volume. The planning target volume was defined as a 2-cm margin in addition to the gross tumor volume and upper 4 cm of the vagina, and 1.5 cm for lymph nodes and vessels. Normal tissue regions of interest included small bowel, large bowel, and bladder. IMRT plans using (1) the limited arc technique (180° arc length) and (2) the extended arc technique (340° arc length) were computed. Dose–volume histograms for normal tissue structures and target were compared between the supine and prone IMRT plans using the paired t test.: ResultsProne positioning on a belly board decreased the small bowel dose in gynecologic pelvic IMRT, and the magnitude of improvement depended on the specific IMRT technique used. With the limited arc technique, prone positioning significantly decreased the irradiated small bowel volume at the 25–50-Gy dose levels compared with supine positioning. Small bowel volumes receiving ≥45 Gy decreased from 19% to 12.5% (p = 0.005) with prone positioning. With the extended arc technique, the decrease in irradiated small bowel volume was less marked, but remained detectable in the 35–45-Gy dose levels. Small bowel volumes receiving ≥45 Gy decreased from 13.6% to 10.1% (p = 0.03) with prone positioning. The effect of prone positioning on large bowel and bladder was variable. Large bowel volumes receiving ≥45 Gy increased with prone positioning from 16.5% to 20.6% (p = 0.02) in the limited arc technique and was unaffected in the extended arc technique.: ConclusionThese preliminary data suggest that prone positioning on a belly board can reduce the small bowel dose further in gynecology patients treated with pelvic RT, and that the dose reduction depends on the IMRT technique used. [Copyright &y& Elsevier]