Improved Tumor Control Related to Radiotherapy Technological Development for Hypopharyngeal Cancer.

OBJECTIVES/HYPOTHESIS: Squamous cell carcinoma of the hypopharynx (SCCHP) is associated with worse survival compared to other head and neck subsites. This report quantifies the impact of technological improvements in radiotherapy (RT) on outcomes over 6 decades. METHODS: Patients with SCCHP receiving curative-intent treatment between 1962 and 2015 were retrospectively reviewed. Kaplan-Meier analyses of freedom from local recurrence (FFLR), progression-free survival (PFS), and overall survival (OS) were compared across treatment eras and radiation techniques. Multivariable Cox proportional hazards modeling was performed to specify the effect of RT technique. RESULTS: One hundred thirty-four patients had a median follow-up of 17 months (IQR = 9-38). There were no differences in staging or use of surgery over time, but use of chemotherapy concurrent with RT increased (P < .001) beginning in the 2000s. The 24-month FFLR using two-dimensional RT (2D-RT), three-dimensional conformal RT (3D-CRT), and intensity-modulated RT (IMRT) was 52%, 55%, and 80%, respectively; 24-month PFS was 39%, 46%, and 73%, respectively; and 24-month OS was 27%, 40%, and 68%, respectively. OS (P = .01), PFS (P = .03), and FFLR (P = 0.02) were improved with IMRT over 2D-RT, and FFLR appeared to be improved over 3D-CRT (P = .06). Controlling for chemotherapy use and other major variables, IMRT produced a strong influence over FFLR (adjusted hazard ratio [HR] = 0.2, 95% confidence interval [CI]: 0.0-1.2, P = .08) and a benefit in OS (adjusted HR = 0.1, 95% CI: 0.0-0.4, P = .005). CONCLUSIONS: Across 6 decades, patient and tumor characteristics remained similar whereas use of chemoradiation increased and IMRT was adopted. The introduction of IMRT was associated with improved FFLR, PFS, and OS, and a reduction in acute toxicity as compared to earlier radiation technologies. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E452-E458, 2021.

Oral isotretinoin and topical retinoid use in a series of young patients with ocular melanoma.

PURPOSE: To describe the first series of six young uveal melanoma (UM) patients with oral isotretinoin and/or topical retinoid therapy prior to diagnosis. OBSERVATIONS: The case series is based on clinical observations at our UM quaternary referral center. Six UM patient cases are reported, ages 16-44 years old. All had been using either oral (isotretinoin) and/or topical (tretinoin or tazarotene) retinoid treatment (3 months-~10 years) prior to or at the time of diagnosis (3 of 6 cases). All patients had ocular complaints on presentation, and the onset of certain symptoms corresponded with the course of retinoids. Other potential risk factors or relevant history included Caucasian background, cone-rod dystrophy and active smoker status (Case 2), family history of UM and pregnancy at time of diagnosis (Case 3), past smoking and possible secondary Chernobyl exposure as a baby (Case 5). All patients were treated with proton beam radiotherapy and currently have no sign of recurrent or metastatic disease. CONCLUSIONS AND IMPORTANCE: Retinoid therapy has been linked to various benign and/or reversible effects on the anterior and posterior eye, though pathophysiology remains not well understood. Uveal melanoma (UM) is a rare cancer diagnosis in young adults. We report here the first case series of young UM patients with a history of retinoid use and ocular complaints. No causal link is claimed and further systematic epidemiologic and biologic study of retinoid therapy and ocular impact may provide additional relevant data, particularly in young ocular melanoma patients.

Technical Note: Feasibility study of titanium markers in choroidal melanoma localization for proton beam radiation therapy.

PURPOSE: The purpose of this study is to explore the feasibility of the use of titanium fiducial markers to minimize the metallic artifact seen with tantalum markers which causes significant distortion on postoperative orbital CT scans. METHOD: We designed and constructed the titanium markers in the shop of Crocker Nuclear Laboratory, UC Davis, CA. The markers were placed on an eyeball phantom. The eyeball was inserted into the Rando phantom in the orbital space. The Rando phantom was imaged with coplanar x rays on Nucletron simulator at UCSF, on digital panel on the eye beam line at CNL eye treatment facility and on CT scanner at UCSF. RESULTS: The titanium markers can be clearly seen on the hard copy of x rays and on digital panel. The CT scan of an orbit using tantalum markers on the right eye and titanium markers on the left eye shows the metal artifact from tantalum markers. Titanium markers show very little distortion on CT images. CONCLUSION: The present study describes these markers and their relative benefit in comparison with tantalum marker, which has been used for localizing ocular tumor for decades.

Temporal Evolution and Dose-Volume Histogram Predictors of Visual Acuity After Proton Beam Radiation Therapy of Uveal Melanoma.

PURPOSE: To perform an in-depth temporal analysis of visual acuity (VA) outcomes after proton beam radiation therapy (PBRT) in a large, uniformly treated cohort of uveal melanoma (UM) patients, to determine trends in VA evolution depending on pretreatment and temporally defined posttreatment VA measurements; and to investigate the relevance of specific patient, tumor and dose-volume parameters to posttreatment vision loss. METHODS AND MATERIALS: Uveal melanoma patients receiving PBRT were identified from a prospectively maintained database. Included patients (n=645) received 56 GyE in 4 fractions, had pretreatment best corrected VA (BCVA) in the affected eye of count fingers (CF) or better, with posttreatment VA assessment at specified post-PBRT time point(s). Patients were grouped according to the pretreatment BCVA into favorable (≥20/40) or unfavorable (20/50-20/400) and poor (CF) strata. Temporal analysis of BCVA changes was described, and univariate and forward stepwise multivariate logistic regression analyses were performed to identify predictors for VA loss. RESULTS: Median VA follow-up was 53 months (range, 3-213 months). At 60-month follow up, among evaluable treated eyes with favorable pretreatment BCVA, 45% retained BCVA ≥20/40, whereas among evaluable treated eyes with initially unfavorable/poor BCVA, 21% had vision ≥20/100. Among those with a favorable initial BCVA, attaining BCVA of ≥20/40 at any posttreatment time point was associated with subsequent maintenance of excellent BCVA. Multivariate analysis identified volume of the macula receiving 28GyE (P<.0001) and optic nerve (P=.0004) as independent dose-volume histogram predictors of 48-month post-PBRT vision loss among initially favorable treated eyes. CONCLUSIONS: Approximately half of PBRT-treated UM eyes with excellent pretreatment BCVA assessed at 5 years after treatment will retain excellent long-term vision. 28GyE macula and optic nerve dose-volume histogram parameters allow for rational treatment planning optimization that may lead to improved visual outcomes. The detailed temporal analysis with intermediate as well as long-term functional prognosis, and the relationship of outcomes with clinical and treatment planning parameters, is critical for informed care of UM patients before and after PBRT.

Long-term disease-specific and cognitive quality of life after intensity-modulated radiation therapy: a cross-sectional survey of nasopharyngeal carcinoma survivors.

BACKGROUND: There is a lack of data on quality of life in long-term survivors of nasopharyngeal carcinoma (NPC) who have been treated with intensity-modulated radiation therapy (IMRT). We characterized long-term disease-specific and cognitive QoL in NPC survivors after IMRT. METHODS: We conducted a cross-sectional study of surviving patients diagnosed and treated for NPC at our center with curative-intent IMRT, with or without chemotherapy. Patients who were deceased, still undergoing treatment, with known recurrent disease, or treated with RT modality other than IMRT were excluded. QoL was measured by FACT-NP and FACT-Cog. RESULTS: Between May and November 2013, 44 patients completed cognitive (FACT-Cog), general (FACT-G), and NPC-specific (NPCS) QoL assessments. Patients were categorized into 4 cohorts based on duration since IMRT (≤2.5, >2.5-6, >6-10, and >10-16 years). There was no significant difference in age (p = 0.20) or stage ((I/II vs III/IV: p = 0.78) among the cohorts. The 4 cohorts differed overall for all QoL measures (ANOVA: p < 0.02 for each), due to improved scores >2.5-6 years post-IMRT compared with ≤2.5 years post-IMRT (post hoc tests: p ≤ 0.04 for each). No differences were observed between >2.5-6 and >6-10 years post-IMRT, but lower mean FACT-Cog and NPCS scores were observed for >10 years compared to >2.5-6 years post-IMRT (post hoc: p < 0.05 for each). CONCLUSIONS: All QoL measures were low during the initial recovery period (≤2.5 years) and were higher by 6 years post-IMRT. At >10 years post-IMRT, lower scores were observed in the domains of NPC-specific and cognitive QoL. Survivors of NPC, even if treated with IMRT, are at risk for detriment in domain-specific QoL measures at very long-term follow-up.

Does radiation dose matter in thyroid cancer?: Patterns of local-regional failure in recurrent and metastatic well-differentiated thyroid cancers treated with dose-painted intensity-modulated radiation therapy.

INTRODUCTION: Due to complex multimodal treatments and a lengthy natural history of disease, the impact of radiation therapy for well-differentiated thyroid cancer (WDTC) is challenging to evaluate. We analysed the effect of dose escalation, as enabled by intensity-modulated radiation therapy (IMRT), on preventing local-regional failure (LRF) of microscopic and macroscopic WDTC. METHOD: We performed a retrospective review of WDTC patients treated with IMRT from 1998-2011. Diagnostic imaging demonstrating first LRF was registered to the simulation CT containing the treated radiation isodose volumes. Areas of disease progression were contoured and the relationships of LRFs with isodose volumes were recorded. RESULTS: Thirty patients had a median follow-up of 56 months (range = 1-139). Seventeen (57%) had gross residual, five (17%) had microscopic residual and eight (27%) had clear margins at the time of IMRT. Nine patients (30%) developed LRF, at a median time of 44 months (range = 0-116). Of these, six (67%) had been radiated to gross disease and one (11%) had microscopic residual. In the seven analysable cases, only one (14%) LRF occurred within the 70 Gy isodose volume. Marginal LRFs were: four (57%) outside 70 Gy, one (14%) outside 60 Gy and one (14%) outside 50 Gy. All but one recurrence (86%) occurred in the perioesophageal region. CONCLUSIONS: Local-regional failure was seen most in patients who had gross disease at the time of IMRT, almost always occurred outside of the 70 Gy volume and was frequently in the area of oesophageal sparing. Meticulous surgical dissection, especially in the perioesophageal region, should be prioritised to prevent long-term LRF.

Long-term Results of the UCSF-LBNL Randomized Trial: Charged Particle With Helium Ion Versus Iodine-125 Plaque Therapy for Choroidal and Ciliary Body Melanoma.

PURPOSE: Relevant clinical data are needed given the increasing national interest in charged particle radiation therapy (CPT) programs. Here we report long-term outcomes from the only randomized, stratified trial comparing CPT with iodine-125 plaque therapy for choroidal and ciliary body melanoma. METHODS AND MATERIALS: From 1985 to 1991, 184 patients met eligibility criteria and were randomized to receive particle (86 patients) or plaque therapy (98 patients). Patients were stratified by tumor diameter, thickness, distance to disc/fovea, anterior extension, and visual acuity. Tumors close to the optic disc were included. Local tumor control, as well as eye preservation, metastases due to melanoma, and survival were evaluated. RESULTS: Median follow-up times for particle and plaque arm patients were 14.6 years and 12.3 years, respectively (P=.22), and for those alive at last follow-up, 18.5 and 16.5 years, respectively (P=.81). Local control (LC) for particle versus plaque treatment was 100% versus 84% at 5 years, and 98% versus 79% at 12 years, respectively (log rank: P=.0006). If patients with tumors close to the disc (<2 mm) were excluded, CPT still resulted in significantly improved LC: 100% versus 90% at 5 years and 98% versus 86% at 12 years, respectively (log rank: P=.048). Enucleation rate was lower after CPT: 11% versus 22% at 5 years and 17% versus 37% at 12 years, respectively (log rank: P=.01). Using Cox regression model, likelihood ratio test, treatment was the most important predictor of LC (P=.0002) and eye preservation (P=.01). CPT was a significant predictor of prolonged disease-free survival (log rank: P=.001). CONCLUSIONS: Particle therapy resulted in significantly improved local control, eye preservation, and disease-free survival as confirmed by long-term outcomes from the only randomized study available to date comparing radiation modalities in choroidal and ciliary body melanoma.

Dosimetric predictors of hypothyroidism in oropharyngeal cancer patients treated with intensity-modulated radiation therapy.

BACKGROUND: Radiation to the neck has long been associated with an elevated risk of hypothyroidism development. The goal of the present work is to define dosimetric predictors of hypothyroidism in oropharyngeal cancer (OPC) patients treated with intensity-modulated radiation therapy. METHODS: Data for 123 patients, with a median follow up of 4.6 years, were retrospectively analyzed. Patients with elevated thyroid-stimulating hormone levels or with a clinical diagnosis were categorized as hypothyroid. Patient demographic parameters, thyroid volume, mean thyroid dose, the percent of thyroid volume receiving minimum specified dose levels (VxxGy), and the absolute thyroid volume spared from specified dose levels (VSxxGy) were analyzed. Normal-tissue complication probability (NTCP) was also calculated using several recently published models. RESULTS: Thyroid volume and many radiation dosimetric parameters were statistically different in the hypothyroid group. For the patients with initial thyroid volumes of 8 cc or greater, several dosimetric parameters were found to define subgroups at statistically significant lower risk of developing hypothyroidism. Patients with VS45 Gy of at least 3 cc, VS50 Gy at least 5 cc, VS50 Gy at least 6 cc, V50 Gy below 45%, V50 Gy below 55%, or mean thyroid dose below 49 Gy had a 28-38% estimated risk of hypothyroidism at 3 years compared to a 55% risk for the entire study group. Patients with a NTCP of less than 0.75 or 0.8, calculated using recently published models, were also observed to have a lower risk of developing hypothyroidism. CONCLUSIONS: Based on long-term follow up data for OPC patients treated with IMRT, we recommend plan optimization objectives to reduce the volume of thyroid receiving over 45 Gy to significantly decrease the risk of developing hypothyroidism.

Risk factors for neovascular glaucoma after proton beam therapy of uveal melanoma: a detailed analysis of tumor and dose-volume parameters.

PURPOSE: To determine neovascular glaucoma (NVG) incidence and identify contributing tumor and dosing factors in uveal melanoma patients treated with proton beam radiation therapy (PBRT). METHODS AND MATERIALS: A total of 704 PBRT patients treated by a single surgeon (DHC) for uveal melanoma (1996-2010) were reviewed for NVG in our prospectively maintained database. All patients received 56 GyE in 4 fractions. Median follow-up was 58.3 months. Analyses included the Kaplan-Meier method to estimate NVG distributions, univariate log-rank tests, and Cox's proportional hazards multivariate analysis using likelihood ratio tests to identify independent risk factors of NVG among patient, tumor, and dose-volume histogram parameters. RESULTS: The 5-year PBRT NVG rate was 12.7% (95% confidence interval [CI] 10.2%-15.9%). The 5-year rate of enucleation due to NVG was 4.9% (95% CI 3.4%-7.2%). Univariately, the NVG rate increased significantly with larger tumor diameter (P<.0001), greater height (P<.0001), higher T stage (P<.0001), and closer proximity to the disc (P=.002). Dose-volume histogram analysis revealed that if >30% of the lens or ciliary body received ≥50% dose (≥28 GyE), there was a higher probability of NVG (P<.0001 for both). Furthermore, if 100% of the disc or macula received ≥28 GyE, the NVG rate was higher (P<.0001 and P=.03, respectively). If both anterior and posterior doses were above specified cut points, NVG risk was highest (P<.0001). Multivariate analysis confirmed significant independent risk factors to include tumor height (P<.0001), age (P<.0001), %disc treated to ≥50% Dose (<100% vs 100%) (P=.0007), larger tumor diameter (P=.01), %lens treated to ≥90% Dose (0 vs >0%-30% vs >30%) (P=.01), and optic nerve length treated to ≥90% Dose (≤1 mm vs >1 mm) (P=.02). CONCLUSIONS: Our current PBRT patients experience a low rate of NVG and resultant enucleation compared with historical data. The present analysis shows that tumor height, diameter, and anterior as well as posterior critical structure dose-volume parameters may be used to predict NVG risk.

Dosimetric evaluation of automatic segmentation for adaptive IMRT for head-and-neck cancer.

PURPOSE: Adaptive planning to accommodate anatomic changes during treatment requires repeat segmentation. This study uses dosimetric endpoints to assess automatically deformed contours. METHODS AND MATERIALS: Sixteen patients with head-and-neck cancer had adaptive plans because of anatomic change during radiotherapy. Contours from the initial planning computed tomography (CT) were deformed to the mid-treatment CT using an intensity-based free-form registration algorithm then compared with the manually drawn contours for the same CT using the Dice similarity coefficient and an overlap index. The automatic contours were used to create new adaptive plans. The original and automatic adaptive plans were compared based on dosimetric outcomes of the manual contours and on plan conformality. RESULTS: Volumes from the manual and automatic segmentation were similar; only the gross tumor volume (GTV) was significantly different. Automatic plans achieved lower mean coverage for the GTV: V95: 98.6 +/- 1.9% vs. 89.9 +/- 10.1% (p = 0.004) and clinical target volume: V95: 98.4 +/- 0.8% vs. 89.8 +/- 6.2% (p < 0.001) and a higher mean maximum dose to 1 cm(3) of the spinal cord 39.9 +/- 3.7 Gy vs. 42.8 +/- 5.4 Gy (p = 0.034), but no difference for the remaining structures. CONCLUSIONS: Automatic segmentation is not robust enough to substitute for physician-drawn volumes, particularly for the GTV. However, it generates normal structure contours of sufficient accuracy when assessed by dosimetric end points.

Can positron emission tomography (PET) or PET/Computed Tomography (CT) acquired in a nontreatment position be accurately registered to a head-and-neck radiotherapy planning CT?

PURPOSE: To quantify the uncertainties associated with incorporating diagnostic positron emission tomography/CT (PET/CT) and PET into the radiotherapy treatment-planning process using different image registration tools, including automated and manual rigid body registration methods, as well as deformable image registration. METHODS AND MATERIALS: The PET/CTs and treatment-planning CTs from 12 patients were used to evaluate image registration accuracy. The PET/CTs also were used without the contemporaneously acquired CTs to evaluate the registration accuracy of stand-alone PET. Registration accuracy for relevant normal structures was quantified using an overlap index and differences in the center of mass (COM) positions. For tumor volumes, the registration accuracy was measured using COM positions only. RESULTS: Registration accuracy was better with PET/CT than with PET alone. The COM displacements ranged from 3.2 +/- 0.6 mm (mean +/- 95% confidence interval, for brain) to 8.4 +/- 2.6 mm (spinal cord) for registration with PET/CT data, compared with 4.8 +/- 1.7 mm (brain) and 9.9 +/- 3.1 mm (spinal cord) with PET alone. Deformable registration improved accuracy, with minimum and maximum errors of 1.1 +/- 0.8 mm (brain) and 5.4 +/- 1.4 mm (mandible), respectively. CONCLUSIONS: It is possible to incorporate PET and/or PET/CT acquired in diagnostic positions into the treatment-planning process through the use of advanced image registration algorithms, but precautions must be taken, particularly when delineating tumor volumes in the neck. Acquisition of PET/CT in the treatment-planning position would be the ideal method to minimize registration errors.

Assessment of carotid artery dose in the treatment of nasopharyngeal cancer with IMRT versus conventional radiotherapy.

PURPOSE: To determine the radiation dose to the carotid artery in nasopharyngeal cancer patients treated with intensity-modulated radiotherapy (IMRT) and to compare it to the dose delivered by a conventional three-field (3F) technique. MATERIALS AND METHODS: Sixteen patients with nasopharyngeal cancer who were treated at UCSF with IMRT were selected for this analysis. 3F plans were reconstructed for comparison. The carotid arteries were retrospectively contoured, and the dose received by each of the 32 carotid arteries was determined for both IMRT and 3F plans. A subset of 8 patients with N0/N1 nodal disease was selected for IMRT replanning using additional constraints to reduce the dose to the arteries. RESULTS: Using the standard prescription doses for IMRT and 3F plans, the dose delivered to 95% of the tumor volume was significantly higher in the IMRT plans, reflecting the greater conformality of this technique. The median mean dose to the carotid arteries was 65.7Gy with IMRT vs. 58.4Gy with 3F (p<0.001). After the application of dose constraints to the carotid arteries, it was possible to reduce the mean carotid dose to 54Gy in the IMRT replans. CONCLUSIONS: IMRT achieves a higher tumoricidal dose and superior clinical target volume coverage, but results in an increase in the carotid artery dose as compared to conventional 3F technique. With careful IMRT planning, it is possible to constrain the carotid dose for a subset of patients with low-risk neck disease. Further study is necessary to quantify the long-term clinical impact of this intervention.

Intensity-modulated chemoradiation for treatment of stage III and IV oropharyngeal carcinoma: the University of California-San Francisco experience.

BACKGROUND: Treatment outcomes for stage III and IV oropharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy without prior surgical resection were reviewed. METHODS: Between April 2000 and September 2004, 71 patients underwent IMRT concurrent with chemotherapy without prior surgical resection for stage III and IV oropharyngeal carcinoma. Chemotherapy was platinum based. The gross tumor volume (GTV) received 70 Gy in 2.12 Gy per fraction. The high-risk clinical tumor volume (CTV) received 59.4 Gy in 1.80 Gy per fraction, and the low-risk CTV received 54 Gy in 1.64 Gy per fraction. RESULTS: With a median follow-up of 33 months, the 3-year local, regional, and locoregional progression-free probabilities were 94%, 94%, and 90%, respectively. The 3-year overall survival estimate was 83%. Locoregional failures occurred in the GTV in 7 patients. Acute grade 3 or 4 toxicity developed in 35 patients. A feeding gastrostomy was placed in 25 patients. Late xerostomia was grade 0 in 16 patients, grade 1 in 31 patients, and grade 2 in 24 patients at last follow-up. No patients experienced grade 3 or 4 late toxicity, except for 1 who developed osteoradionecrosis of the mandible. CONCLUSIONS: Excellent local and regional control was achieved with IMRT and concurrent chemotherapy without prior surgical resection in the treatment of stage III and IV oropharyngeal carcinoma. Significant sparing of the parotid glands and other critical normal tissues was possible using IMRT with moderate acute toxicities and minimal severe late effects.

Detection of treatment setup errors between two CT scans for patients with head and neck cancer.

Accuracy of treatment setup for head and neck patients undergoing intensity-modulated radiation therapy is of paramount importance. The conventional method using orthogonal portal images can only detect translational setup errors while the most frequent setup errors for head and neck patients could be rotational errors. With the rapid development of image-guided radiotherapy, three-dimensional images are readily acquired and can be used to detect both translational and rotational setup errors. The purpose of this study is to determine the significance of rotational variations between two planning CT scans acquired for each of eight head and neck patients, who experienced substantial weight loss or tumor shrinkage. To this end, using a rigid body assumption, we developed an in-house computer program that utilizes matrix transformations to align point bony landmarks with an incremental best-fit routine. The program returns the quantified translational and rotational shifts needed to align the scans of each patient. The program was tested using a phantom for a set of known translational and rotational shifts. For comparison, a commercial treatment planning system was used to register the two CT scans and estimate the translational errors for these patients. For the eight patients, we found that the average magnitudes and standard deviations of the rotational shifts about the transverse, anterior-posterior, and longitudinal axes were 1.7 +/- 2.3 degrees, 0.8 +/- 0.7 degrees, and 1.8 +/- 1.1 degrees, respectively. The average magnitudes and standard deviations of the translational shifts were 2.5 +/- 2.6 mm, 2.9 +/- 2.8 mm, 2.7 +/- 1.7 mm while the differences detected between our program and the CT-CT fusion method were 1.8 +/- 1.3 mm, 3.3 +/- 5.4 mm, and 3.0 +/- 3.4 mm in the left-right, anterior-posterior, and superior-inferior directions, respectively. A trend of larger rotational errors resulting in larger translational differences between the two methods was observed. In conclusion, conventional methods used for verifying patient positioning may misinterpret rotational shifts as translational shifts, and our study demonstrated that rotational errors may be significant in the treatment of head and neck cancer.

Simplifying intensity-modulated radiotherapy plans with fewer beam angles for the treatment of oropharyngeal carcinoma.

The first aim of the present study was to investigate the feasibility of using fewer beam angles to improve delivery efficiency for the treatment of oropharyngeal cancer (OPC) with inverse-planned intensity-modulated radiation therapy (IP-IMRT). A secondary aim was to evaluate whether the simplified IP-IMRT plans could reduce the indirect radiation dose. The treatment plans for 5 consecutive OPC patients previously treated with a forward-planned IMRT (FP-IMRT) technique were selected as benchmarks for this study. The initial treatment goal for these patients was to deliver 70 Gy to > or = 95% of the planning gross tumor volume (PTV-70) and 59.4 Gy to > or = 95% of the planning clinical tumor volume (PTV-59.4) simultaneously. Each case was re-planned using IP-IMRT with multiple beam-angle arrangements, including four complex IP-IMRT plans using 7 or more beam angles, and one simple IMRT plan using 5 beam angles. The complex IP-IMRT plans and simple IP-IMRT plans were compared to each other and to the FPIMRT plans by analyzing the dose coverage of the target volumes, the plan homogeneity, the dose-volume histograms of critical structures, and the treatment delivery parameters including delivery time and the total number of monitor units (MUs). When comparing the plans, we found no significant difference between the complex IP-IMRT, simple IP-IMRT, and FP-IMRT plans for tumor target coverage (PTV-70: p = 0.56; PTV-59.4: p = 0.20). The plan homogeneity, measured by the mean percentage isodose, did not significantly differ between the IP-IMRT and FP-IMRT plans (p = 0.08), although we observed a trend toward greater inhomogeneity of dose in the simple IP-IMRT plans. All IP-IMRT plans either met or exceeded the quality of the FP-IMRT plans in terms of dose to adjacent critical structures, including the parotids, spinal cord, and brainstem. As compared with the complex IP-IMRT plans, the simple IP-IMRT plans significantly reduced the mean treatment time (maximum probability for four pairwise comparisons: p = 0.0003). In conclusion, our study demonstrates that, as compared with complex IP-IMRT, simple IP-IMRT can significantly improve treatment delivery efficiency while maintaining similar target coverage and sparing of critical structures. However, the improved efficiency does not significantly reduce the total number of MUs nor the indirect radiation dose.

Carcinomas of the paranasal sinuses and nasal cavity treated with radiotherapy at a single institution over five decades: are we making improvement?

PURPOSE: To compare clinical outcomes of patients with carcinomas of the paranasal sinuses and nasal cavity according to decade of radiation treatment. METHODS AND MATERIALS: Between 1960 and 2005, 127 patients with sinonasal carcinoma underwent radiotherapy with planning and delivery techniques available at the time of treatment. Fifty-nine patients were treated by conventional radiotherapy; 45 patients by three-dimensional conformal radiotherapy; and 23 patients by intensity-modulated radiotherapy. Eighty-two patients (65%) were treated with radiotherapy after gross total tumor resection. Nineteen patients (15%) received chemotherapy. The most common histology was squamous cell carcinoma (83 patients). RESULTS: The 5-year estimates of overall survival, local control, and disease-free survival for the entire patient population were 52%, 62%, and 54%, respectively. There were no significant differences in any of these endpoints with respect to decade of treatment or radiotherapy technique (p > 0.05, for all). The 5-year overall survival rate for patients treated in the 1960s, 1970s, 1980s, 1990s, and 2000s was 46%, 56%, 51%, 53%, and 49%, respectively (p = 0.23). The observed incidence of severe (Grade 3 or 4) late toxicity was 53%, 45%, 39%, 28%, and 16% among patients treated in the 1960s, 1970s, 1980s, 1990s, and 2000s, respectively (p = 0.01). CONCLUSION: Although we did not detect improvements in disease control or overall survival for patients treated over time, the incidence of complications has significantly declined, thereby resulting in an improved therapeutic ratio for patients with carcinomas of the paranasal sinuses and nasal cavity.

A phase II study of fixed-dose rate gemcitabine plus low-dose cisplatin followed by consolidative chemoradiation for locally advanced pancreatic cancer.

PURPOSE: The optimal strategy for treating locally advanced pancreatic cancer remains controversial, including the respective roles and timing of chemotherapy and radiation. We conducted a Phase II nonrandomized trial to evaluate sequential chemotherapy followed by chemoradiation in this patient population. METHODS AND MATERIALS: Chemotherapy naive patients with locally advanced pancreatic adenocarcinoma were treated with fixed-dose rate gemcitabine (1,000 mg/m(2) at 10 mg/m(2)/min) plus cisplatin 20 mg/m(2) on Days 1 and 15 of a 28-day cycle. Those without evidence of extrapancreatic metastases after six cycles of chemotherapy received radiation (5,040 cGy over 28 fractions) with concurrent capecitabine (800 mg/m(2) orally twice daily on the day of radiation) as a radiosensitizer. RESULTS: A total of 25 patients were enrolled with a median follow-up time of 656 days. Twelve patients (48%) successfully received all six cycles of chemotherapy plus chemoradiation. Eight patients (32%) progressed during chemotherapy, including 7 with extrapancreatic metastases. Grade 3/4 hematologic toxicities were uncommon. Two patients sustained myocardial infarctions during chemotherapy, and 4 were hospitalized for infectious complications, although none in the setting of neutropenia. Median time to progression was 10.5 months and median survival was 13.5 months, with an estimated 1-year survival rate of 62%. Patients receiving all components of therapy had a median survival of 17.0 months. CONCLUSIONS: A strategy of initial fixed-dose rate gemcitabine-based chemotherapy, followed by chemoradiation, shows promising efficacy for treatment of locally advanced disease. A substantial proportion of patients will be identified early on as having extrapancreatic disease and spared the potential toxicities associated with radiation.

Nonfunctioning parathyroid carcinoma: case report and review of literature.

OBJECTIVE: To report a case of nonfunctioning parathyroid carcinoma that was incidentally found during a thyroidectomy for multinodular goiter. METHODS: We present a case report, detailing the clinical course and histologic findings in a patient with a nonfunctional parathyroid carcinoma. The related literature is also reviewed. RESULTS: A 67-year-old woman presented with a 30-year history of a multinodular goiter that was symptomatic. A total thyroidectomy was performed. Histologic examination revealed not only a multinodular thyroid but also a mass in the left lobe, which was diagnostic of a parathyroid carcinoma. Serum calcium and parathyroid hormone levels were normal postoperatively. Eleven months after the initial operation, a suprasternal mass developed, and she underwent neck reexploration and subtotal resection of an invasive recurrent nonfunctioning parathyroid carcinoma. The serum parathyroid hormone and calcium levels were normal before and after the operation. Postoperatively, the patient underwent radiation therapy. Twenty-three months after the initial operation, a computed tomographic scan of the chest revealed an interval increase in size of a nodule in the left lower lobe of the lung, and 30 months after her initial operation, she underwent resection of an isolated, 1-cm (greatest diameter), metastatic parathyroid carcinoma in the left lower lobe of the lung. The patient is currently doing well without evidence of recurrent disease. CONCLUSION: Nonfunctioning parathyroid carcinomas are difficult to diagnose and to treat. Recurrent disease after operation is common, and radiation therapy may help stabilize tumor growth. Patients with nonfunctioning parathyroid carcinomas appear to have a poorer prognosis than do those with functioning parathyroid cancers.

The role of postoperative radiation therapy in carcinoma ex pleomorphic adenoma of the parotid gland.

PURPOSE: To evaluate the impact of postoperative radiation therapy on the clinical course of patients with carcinoma ex pleomorphic adenoma of the parotid gland. METHODS AND MATERIALS: Between 1960 and 2004, 63 patients were treated with definitive surgery for carcinoma ex pleomorphic adenoma of the parotid gland. Forty patients (63%) received postoperative radiation therapy to a median dose of 60 Gy (range, 45-71 Gy). Adenocarcinoma (29 patients), salivary duct carcinoma (16 patients), and adenoid cystic carcinoma (9 patients) were the most common malignant subtypes. Pathologic T -stage was: 16% T1, 33% T2, 32% T3, and 19% T4. Twenty-one patients (33%) had microscopically positive margins and 39 (62%) had perineural invasion. Median follow-up was 50 months (range, 2-96 months). RESULTS: The use of postoperative therapy significantly improved 5-year local control from 49% to 75% (p = 0.005) and was associated with an improvement in survival among patients without evidence of cervical lymph node metastasis (p = 0.01). A Cox proportional hazard model identified pathologic involvement of cervical lymph nodes as an independent predictor of overall survival. Overall survival was 16% for patients with pathologic N-positive disease compared with 67% for those whose lymph node status was negative or unknown (p = 0.001). CONCLUSION: Surgery followed by postoperative radiation should be considered the standard of care for patients with carcinoma ex pleomorphic adenoma.