Management algorithm for HIV-associated parotid lymphoepithelial cysts.

We report an evidence-based management algorithm for benign lymphoepithelial cysts (BLEC) of the parotid glands in HIV patients based on long-term outcomes after radiation therapy. From 1987 to 2013, 72 HIV-positive patients with BLEC of the parotid glands treated at our institutions were identified and their medical records were reviewed and analyzed. The primary endpoint of our study was to determine a dose response in HIV patients with BLEC. In group A (≤18 Gy), which received a median dose of 10 Gy (8-18), overall response (OvR), complete response (CR), partial response (PR), and local failure (LF) was experienced by 7, 7, 0, and 93 %, respectively. In group B (≥22.5 Gy), which received a median dose of 24 Gy (22.5-30), OvR, CR, PR, and LF was experienced by 88, 65, 23, and 12 %. Logistic regression revealed that higher dose (≥22.5 Gy) predicted for cosmetic control (p = 0.0003). Multiple regression analysis revealed higher dose predicted for cosmetic control (p = 0.0001) after adjusting for confounding variables (age, gender, race, HAART use, BLEC duration, and fractionation size). No patients in either group experienced RTOG grade ≥3 toxicities. A radiation dose of 24 Gy delivered in 12-16 fractions of 1.5-2 Gy per fraction provides long-term cosmetic control in HIV-positive patients with BLEC of the parotid glands.

Postoperative radiation therapy for parotid pleomorphic adenoma with close or positive margins: treatment outcomes and toxicities.

AIM: To evaluate the locoregional control and treatment toxicity of patients with pleomorphic adenoma after resection with close or positive margins followed by postoperative radiation therapy (PORT). PATIENTS AND METHODS: Between 2002 and 2011, twenty-one patients underwent PORT at the Mount Sinai Beth Israel Medical Center for pleomorphic adenoma of the parotid with close or positive margins. Four out of the 21 patients (19%) had recurrent lesions. The median dose was 57.6 Gy (range 55.8-69.96) delivered at 1.8-2.12 Gy/fraction. Treatment and follow-up data were retrospectively analyzed for locoregional control as well as acute- and late-treatment toxicities. Actuarial survival analysis was also performed. RESULTS: Twelve women and 9 men with a median age of 46 (26-65) at PORT were included in this study. Eighty-one percent of the cohort had positive resection margins while 19% had close margins. At a median follow-up of 92 months, 19/21 patients (90%) had locoregional control. Two patients who failed had primary lesions which recurred locally, and initially had positive margins. The two recurrences occurred at 8 months and 12 months. Acute Radiation Therapy Oncology Group (RTOG) grade 1 and 2 toxicities were experienced by 11 (52%) and 4 (19%) patients, respectively, while 2 (10%) experienced late RTOG grade 1 toxicities. No patients experienced any grade 2-4 late toxicities. Actuarial survival was 100%. CONCLUSION: PORT for patients with pleomorphic adenoma of the parotid gland after resection with close or positive margins results in excellent locoregional control and low treatment-related morbidity.

Initial experience with oropharynx-targeted radiation therapy for metastatic squamous cell carcinoma of unknown primary of the head and neck.

AIM: Metastasis of unknown primary (MUP) is commonly treated with radiation therapy (RT) to the entire mucosal surfaces and bilateral neck nodes (LN). We report outcomes of oropharynx-targeted RT, retropharyngeal nodes (RPN) and bilateral LN in this context. PATIENTS AND METHODS: Single-Institution retrospective study of 68 patients. Forty percent were treated with intensity-modulated radiation therapy (IMRT). Fifty-six percent received concurrent chemoradiotherapy (CCRT). The median age was 58 years, 82% were Caucasian, and 75% males. Stage III disease was present in 9%, stage IVA in 75% and IVB in 16%. RESULTS: At a median follow-up of 3.5 years, the actuarial locoregional control was 95.5%. The emergence of primary developed in 1patient (1.5%) and 2patients (3%) failed in the neck. The median time-to-locoregional failure (LRF) was 18 months. Actuarial long-term RT toxicity was grade 1 xerostomia (68%), dysphagia (35%), neck stiffness (15%) and trismus (6%). CONCLUSION: RT to the oropharynx, RPN, and bilateral neck provides excellent oncological and functional outcomes in MUP in non-Asian patients. Sparing the mucosal surfaces of the nasopharynx, hypopharynx, and larynx seems reasonable without impacting on survival and locoregional control.

Five-year outcomes of squamous cell carcinoma of the tonsil treated with radiotherapy.

PURPOSE: To retrospectively review our single institution experience of patients with tonsillar squamous cell carcinoma. MATERIAL AND METHODS: Between 1999 and 2005, a total of 79 patients were identified. Stage distribution was as follows: stages I-II, III, IVA, and IVB were in 6, 14, 43, and 16 patients, respectively. Sixty-three patients (80%) were male. Median age was 55.5 years. Treatment generally consisted of external beam radiation therapy (RT) (median dose, 70 Gy), concomitant chemotherapy (CCRT) (cisplatin 100 mg/m on days 1, 22, and 43), and neck dissection (ND), and was administered as follows: stages I/II, 6 patients received RT alone; stages III/IVA, 20, 5, and 32 patients received RT alone, CCRT, and CCRT followed by ND, respectively; stage IVB, 9 and 7 patients received CCRT and CCRT plus ND, respectively. RESULTS: After a median follow-up of 56 months (range, 12 to 122 mo), the 5-year local control (LC), regional control (RC), distant control (DC), and overall survival (OS) by stage were as follows: stage I-II 100%, 100%, 100%, 100%; stage III-IVA 98%, 96%, 95%, and 88%; stage IVB 100%, 100%, 69%, and 66%, respectively. Among stage IVB patients, DC was significantly lower (P=0.01) and a trend toward lower OS was noted (P=0.08). Long-term percutaneous endoscopic gastrostomy dependence was noted in 3% of them who had received CCRT. The effect of both chemotherapy and ND on treatment outcomes was analyzed; in stage III/IVA patients treated with or without chemotherapy, LC was 97% and 100% (P=0.43); RC was 92% and 100%(P=0.27); and DC was 91% and 94% (P=0.92), respectively. In stage III/IVA, patients treated with CCRT with or without ND, RC was 100% and 88%, respectively (P=0.087). CONCLUSIONS: Primary radiotherapy with or without CCRT followed by ND provides excellent tumor control with acceptable toxicity in treating squamous cell carcinoma of the tonsil.

Long-term outcome of seropositive HIV patients with head and neck squamous cell carcinoma treated with radiation therapy and chemotherapy.

AIM: To report the outcome of radiation therapy (RT) +/- chemotherapy in HIV-seropositive patients with Head and Neck Squamous Cell Carcinoma (HNSCC). PATIENTS AND METHODS: This is the largest single-Institution retrospective study to date, consisting of 73 HIV patients with HNSCC treated from January 1997-2010. The median age at RT, HIV diagnosis and the duration of patients being HIV seropositive were 51, 34, and 11 years, respectively. Seventy patients had SCC and one had submandibular salivary duct carcinoma. Stages I-II, III and IVA/B were: 22%, 27% and 51%, respectively. Primary cancer sites comprised the larynx (37%), oropharynx (32%), oral cavity (13%), hypopharynx (7%), nasopharynx (4%), unknown primary (MUP) (4%), nasal cavity (3%), and submandibular salivary duct (1%). All patients had an ECOG performance scale of ≤1 and were treated with RT +/- chemotherapy. Fifty patients (70%) were on highly active anti-retroviral therapy (HAART) during treatment, and the median CD4 count was 290 (range: 203-1142). Median dose of 70, 63, and 54 Gy were delivered to the gross disease, high-risk neck, and low-risk neck respectively. Median duration of treatment was 52 (range: 49-64) days. Twelve patients (17%) underwent neck dissection for N3 disease. RESULTS: After a median follow-up of 47 months (range: 7-140), the 4-year locoregional control (LRC) and overall survival (OS) were 69% and 55% respectively. Seven patients (10%) developed second primary sites within the first 5 years of completing RT (2 anal SCCs and 5 HNSCCs). The LRC for Stages III/IV larynx and oropharynx SCC (which represent the majority of the cohort) were 76% and 70%, respectively. Chemo/RT-related late toxicities were dysphagia of grade≤2, 3, and 4 found in 74%, 15% and 11% of patients, respectively. Hoarseness (grade 1) was reported in 10% of patients; no patient experienced grade ≥2. Xerostomia grade ≤2, and 3 was found in 77% and 23% of patients, respectively. A Chi-square test and univariate analysis showed statistically significant relationships between LRC and duration of RT (p<0.001), as well as positive trends for weight loss (<10%) and absence of second malignancy. CONCLUSION: Definitive RT +/- chemotherapy for HIV-seropositive patients with HNSCC appears to be less effective compared to the observed rates of LRC and OS of other HNSCC without HIV. Due to advances in the HAART which prolongs HIV patients' survival, it is extremely important to establish better treatment strategies to improve therapeutic ratio in this growing patient population.

25-year follow-up of HIV-positive patients with benign lymphoepithelial cysts of the parotid glands: a retrospective review.

AIM: To report long-term outcomes for HIV-positive patients who underwent radiation therapy (RT) for benign lymphoepithelial cysts (BLEC) of the parotid glands. PATIENTS AND METHODS: In this single institution retrospective study of HIV-associated BLEC of the parotids, the medical records of 37 HIV-positive patients who were treated with RT between 1987-2012 were reviewed. Patients were stratified into two groups; group A consisted of 15 patients (40.5%) who received a total dose of ≤18Gy, with a median dose 10 Gy (range 8-18Gy), and group B consisted of 22 patients (59.5%) who received a total dose of 24 Gy. In addition to dosing information, additional patient data were collected, including demographics, HAART compliance, follow-up, and re-treatment status. RESULTS: The median age at the time of treatment was 41 (range=7-70) years. With a median follow-up of 35 (range=12-75) months for the entire cohort, the complete response (CR) and partial response (PR) rates were 35% and 8%, respectively. All but one of 15 patients in Group A (lower total dose) eventually experienced local failure with the re-emergence of parotid hypertrophy. Among the patients in group B (higher total dose of 24 Gy), 55%, 13%, and 32% experienced CR, PR, and LF, respectively. Median times to failure in groups A and B were 7 and 20 months, respectively (p<0.0001). Similarly, logistic regression test revealed the higher dose to be associated with better response rate (i.e. CR or PR) (p<0.0001), which was also statistically significant (p=0.03) after adjusting for confounding variables (age, race, gender, HAART use, and fractionation). CONCLUSION: A total dose of 24 Gy continues to be recommended for durable cosmetic control of BLEC of the parotid glands that is associated with HIV-seropositivity.

Comprehensive head and neck radiotherapy dose-volume constraints do not apply to smaller volumes.

AIM: To investigate the impact of definitive radiation therapy (RT) in the management of early glottic cancer on clinical RT-induced dysphagia (RID) and carotid vasculopathy (RICV). PATIENTS AND METHODS: This is a single-institution retrospective study. From January 1997 to 2010, 253 patients, with early glottic cancer, underwent RT with (60)Co or LINAC-6 MV photons. RT fields with wedge pair and daily 5-mm bolus were applied in all patients treated with 6-MV photons to avoid under-dose of the anterior laryngeal structures. The whole larynx (LX), pharyngeal constrictors (PCs), and carotid arteries (CA) were contoured and dose-volume histograms (DVHs) were generated to assess the delivered dose. The median age of patients was 65 years (range; 28-93), Caucasians were 80%, males were 87%, and 23% had T2 lesions. RESULTS: After a median follow-up of seven years (range; 1.5-12), the median dose and fraction size delivered to the LX were 63 and 2.25 Gy, respectively. The mean doses to the LX, PC, and CA were 57 Gy delivered to 34 cm(3), 54 Gy to 15 cm(3), and 60 Gy to 4 cm(3), respectively. The LX, PC and CA V60 and V65 were (77 and 71), (70 and 52) and (84 and 51), respectively. Patients with acute dysphagia grades 1, 2, and 3 or more were 81, 19%, and zero, respectively; none had clinically RID or RICV. CONCLUSION: Small-volume RT up to 67.5 Gy at 2.25 Gy per fraction, is not a predictor of RID or RICV. Separate delineation of the aforementioned critical structures, as well as others, may better identify dose tolerances to maintain function and further prioritize the importance of structures in RID and RICV.

Computerized tomography-based radiotherapy improves heterotopic ossification outcomes.

PURPOSE: To report the impact of computerized tomography (CT) based radiotherapy (RT) on heterotopic ossification (HO) outcomes. METHODS: This is a single institution, retrospective study of 532 patients who were treated for traumatic acetabular fractures (TAF). All patients underwent open-reduction internal-fixation (ORIF) of the TAF followed by RT for HO prophylaxis. Postoperative RT was delivered within 72h, in a single fraction of 7Gy. The patients were divided into 2 groups based on RT planning: CT (A) vs. clinical setup (B). RESULTS: At a median follow up of 8years the incidence of HO was 21.6%. Multivariate regression analysis revealed that group (A) vs. (B) had HO incidence of 6.6% vs. 24.6% (p<0.001), respectively. Furthermore, HO Brooker grade ≥3 was observed in 2.2% vs. 10.8% (p=0.007) in group (A) vs. (B), respectively. Thus, the odds of developing HO and Brooker grades ≥3 were 4.7 and 4.5 times higher, respectively, in patients who underwent clinical setup. CONCLUSION: Our data suggest that using CT based RT allowed more accurate delineation of the tissues and better clinical outcomes. Although CT-based RT is associated with additional cost the efficacy of CT-based RT reduces the risk of HO, thereby decreasing the need for additional surgical interventions.

Exploration of the role of radiotherapy in the management of early glottic cancer with complete carotid artery occlusion.

BACKGROUND: The aim of this study was to compare intensity-modulated radiation therapy (IMRT) vs. 2D and 3D radiotherapy (RT) in the treatment of T1 glottic squamous cell carcinoma in an effort to highlight the advantages of IMRT in this particular clinical situation. CASE REPORT: We present the case of an 82-year-old female patient with T1 left true vocal cord squamous cell carcinoma and complete occlusion of the left carotid artery resulting in multiple strokes. The patient underwent definitive RT with 63 Gy (28 × 2.25 Gy). 3 plans were generated: 2D RT, 3D RT, and IMRT. The right carotid artery (Rt.CA) mean dose was 865, 2,065, and 4,268 cGy for IMRT, 3D RT, and 2D RT, respectively. The inferior pharyngeal constrictor (IPC) mean dose was 5,341, 6,456, and 6,451 cGy for IMRT, 3D RT, and 2D RT, respectively. IMRT provided the best homogeneity but at a higher cost and with prolonged treatment time. CONCLUSION: IMRT provided the finest planning target volume coverage with minimal Rt.CA and IPC doses. IMRT is recommended in certain clinical scenarios which are not manageable with other techniques.

Lack of adjuvant radiotherapy may increase risk of retropharyngeal node recurrence in patients with squamous cell carcinoma of the head and neck after transoral robotic surgery.

Purpose. Transoral robotic surgery (TORS) has increased in popularity in the management of squamous cell carcinoma of the head and neck. However, TORS does not address the neck or retropharyngeal nodes (RPN). In the current report, we highlight the impact of the lack of adjuvant radiotherapy on RPN recurrence after TORS. Materials and Methods. A 58-year-old Caucasian male presented with squamous cell carcinoma of the head and neck of unknown primary. He was offered radiotherapy as a definitive management for clinical stage T0N2aM0, stage IVA, but he opted to left neck dissection. Follow-up PET-CT scan revealed recurrence in the left base of tongue and right level II lymph node. He was offered radiotherapy which he declined and opted to TORS and right neck dissection. Follow-up PET-CT scan showed recurrence in left RPN for which he underwent salvage concurrent chemoradiotherapy to 70 Gy. Results. After a followup of 9 months from the date of salvage chemoradiotherapy completion, the patient is with no evidence of disease. Conclusions. TORS followed by adjuvant radiotherapy seems reasonable in the context of squamous cell carcinoma of the head and neck due to the odds of RPN involvement. Further reports are warranted to optimize post-TORS adjuvant treatment.

Clinical validation and applications for CT-based atlas for contouring the lower cranial nerves for head and neck cancer radiation therapy.

OBJECTIVES: Radiation induced cranial nerve palsy (RICNP) involving the lower cranial nerves (CNs) is a serious complication of head and neck radiotherapy (RT). Recommendations for delineating the lower CNs on RT planning studies do not exist. The aim of the current study is to develop a standardized methodology for contouring CNs IX-XII, which would help in establishing RT limiting doses for organs at risk (OAR). METHODS: Using anatomic texts, radiologic data, and guidance from experts in head and neck anatomy, we developed step-by-step instructions for delineating CNs IX-XII on computed tomography (CT) imaging. These structures were then contoured on five consecutive patients who underwent definitive RT for locally-advanced head and neck cancer (LAHNC). RT doses delivered to the lower CNs were calculated. RESULTS: We successfully developed a contouring atlas for CNs IX-XII. The median total dose to the planning target volume (PTV) was 70Gy (range: 66-70Gy). The median CN (IX-XI) and (XII) volumes were 10c.c (range: 8-12c.c) and 8c.c (range: 7-10c.c), respectively. The median V50, V60, V66, and V70 of the CN (IX-XI) and (XII) volumes were (85, 77, 71, 65) and (88, 80, 74, 64) respectively. The median maximal dose to the CN (IX-XI) and (XII) were 72Gy (range: 66-77) and 71Gy (range: 64-78), respectively. CONCLUSIONS: We have generated simple instructions for delineating the lower CNs on RT planning imaging. Further analyses to explore the relationship between lower CN dosing and the risk of RICNP are recommended in order to establish limiting doses for these OARs.

Tolerance and toxicity of primary radiation therapy in the management of seropositive HIV patients with squamous cell carcinoma of the head and neck.

OBJECTIVES/HYPOTHESIS: To report tolerance and toxicity of radiotherapy (RT) with or without chemotherapy in HIV seropositive patients with squamous cell carcinoma of the head and neck (SCCHN). METHODS: This is a single institution retrospective study of 73 HIV seropositive patients with SCCHN treated from January 1997 through 2010. Stages I, II, III, and IV were 8%, 10%, 24%, and 58%, respectively. The median age at RT, HIV diagnosis. and the duration of HIV seropositive were 51 (32-72), 34 (25-50), and 11 (6-20) years, respectively. Patients were treated definitively with RT alone (35%) or concurrent chemo-RT (65%). Median dose of 70 Gy (66-70) was delivered to the gross disease. Median duration of treatment was 52 (49-64) days. Fifty patients (70%) were on HAART. RESULTS: RT± chemotherapy induced acute toxicity was: median weight loss 20 pounds (6-40), 100% developed dysgeusia and xerostomia (grades 1-3). Acute mucositis and dysphagia/odynophagia grades ≤ 2 and 3 were 83% and 17%, respectively. Treatment breaks in excess of 10, 7, and 3 days were found in 5%, 13%, and 15% of patients, respectively. With a median follow-up of 4 years (2-12) the RT ±chemotherapy induced late dysphagia and xerostomia grades >2 were 26% and 23% of patients, respectively. CONCLUSION: Our data show that primary RT ±chemotherapy for HIV seropositive SCCHN is less tolerated compared to the historical data for SCCHN without HIV. LEVEL OF EVIDENCE: 2b.

Radiation therapy for Benign Lymphoepithelial Cysts of parotid glands in HIV patients.

OBJECTIVES/HYPOTHESIS: To report the long-term outcomes of radiation therapy (RT), and the impact of fractionation size and RT duration on HIV patients with Benign Lymphoepithelial Cysts (BLEC) of the parotid glands. METHODS: From January 2000 to 2011, 30 patients were eligible for our single institution retrospective study. Both parotids were treated with 24 Gy via RT. The median age at RT, HIV diagnosis, and duration of HIV seropositive was 45 years (28-64), 38 years (23-53), and 11 years (6-35), respectively. Patients were stratified into two groups. Group A and B received 2Gyx12 and 1.5Gyx16, respectively. RESULTS: After a median follow-up of 66 months (12-141), the overall response (OvR) was 93% of the patients. Specifically, complete response (CR) and partial response (PR) were 80% and 13%, respectively. In group A, 100% had CR. Treatment failure was 7% and all were in group B, which was mainly due to poor compliance. A Chi-square test showed significant relationship between OvR and RT duration (P <0.001), and a positive trend between CR and fraction size of 2 Gy (P = 0.053). All acute toxicities were grade ≤ 2, specifically mucositis (48%), xerostomia (45%), skin erythema (41%), and altered taste (14%). Two patients (6.7%) experienced long-term grade 1 xerostomia. CONCLUSION: RT provides a sustained long-term cosmetic control for BLEC of the parotid glands in HIV patients. Failures are uncommon, and the late side effects have been negligible.

The impact of computed tomography on early glottic cancer outcomes.

PURPOSE: Aim of this study was to evaluate the impact of computed tomography (CT)-based simulation and planning on early glottic cancer outcomes and toxicity. METHODS: This is a single-institution retrospective study of 253 patients with T1-2 glottic cancer who underwent radiation therapy (RT) from January 1998-2010. Group A (80%) underwent 2-dimensional RT (2DRT) and group B (20%) 3-dimensional RT (3DRT). 76% of patients in group A and 84% in group B had T1 cancer. The median dose and fraction size were 63 Gy and 2.25 Gy, respectively. RESULTS: With a median follow-up of 83, 93, and 30 months for the whole cohort, group A and B, respectively, the loco-regional control (LRC) was 97.6%. The rate of LRC for T1 disease was 99.5% and for T2 disease 91%. According to the RT modality, rates of LRC were 99.4 and 100% in groups A and B for T1, and 89.8 and 100% for T2. Long-term toxicity was negligible in both groups. Kaplan-Meier Curve showed the 5-year cause-specific survival to be 100%. Chi-square and multivariate analysis tests showed a significant relationship between CT simulation (3DRT) and LRC (p < 0.0001). CONCLUSION: CT-based simulation and planning provided better LRC and less acute side effects compared to 2DRT.

The influence of pregnancy on heterotopic ossification post-displaced acetabular fractures surgical repair.

Pregnancy is associated with maternal bone mineral density loss and modulation of calcium metabolism. We hypothesized that pregnancy may decrease the risk of heterotopic ossification (HO) after trauma. This is a single-institution, University of Mississippi Medical Center, retrospective study investigating the effect of pregnancy on the incidence HO after surgical repair (SR) of displaced acetabular fractures. Between January 1998 and 2010, 257 non-pregnant women (Group A) and 16 pregnant women (Group B) were identified. All the non-pregnant women received radiation therapy (RT) ± indomethacin. None of the pregnant women in group B received any prophylaxis. After a median follow-up of 6.6 years the incidence of HO in all patients was 27% (75/273). In Group A, non-pregnant, women who received RT ± indomethacin, 29% developed HO; HO risk was 0.4. In Group B, 16 pregnant patients, only one developed HO (6%); HO risk was 0.06. Thus, the risk of HO appears to be nearly six-fold higher in non-pregnant women despite prophylactic RT ± indomethacin. Our data suggest that pregnancy may be associated with a reduced risk of HO after SR of displaced acetabular fractures. Further analysis with a larger pregnant patient sample is necessary to confirm this finding.

Long-term follow-up and pattern of failure for T1-T2 glottic cancer after definitive radiation therapy.

PURPOSE: To evaluate the impact of radiation therapy (RT) on the long-term outcomes and pattern of failure for T1-2 glottic cancer. MATERIALS AND METHODS: This is a single-institution, retrospective study. From January (1997 to 2010), 253 patients with early glottic cancer underwent RT by 2-dimensional or 3-dimensional RT with Co or linear accelerator. Appropriate daily bolus was applied with linear accelerator-based RT to avoid under dosage of the anterior commissure. RESULTS: A total of 253 patients with T1-T2 glottic cancer were treated with definitive RT. The median age was 65 and males made up 87% of the population. T1 was 77% of the population. The median dose and fraction size were 63 and 2.25 Gy, respectively. After a median follow-up of 83 months, the locoregional control (LRC) for the whole cohort was 98%. Specifically, LRCs for T1 (195 patients) and T2 (58 patients) were 99.5% and 91%, respectively. Kaplan-Meier curve shows the 5-year cause-specific survival to be 100%. CONCLUSIONS: Single-modality RT provides an excellent and effective treatment for T1-T2 glottic cancer with remarkable functional preservation and 5-year LRC of 98% with negligible long-term toxicity.

Trimodality management of sinonasal undifferentiated carcinoma and review of the literature.

OBJECTIVE: Sinonasal undifferentiated carcinoma (SNUC) is a rare and aggressive malignancy with optimal management remains unclear. We performed a review of the impact of trimodality approach on SNUC outcome. METHODS: This is a single-institution retrospective study of 18 patients, who were managed between 1997 and 2009. The median age at presentation was 52 years (28 to 82). Nine patients (50%) were female. Three patients had stage II disease and underwent surgery alone, 12 had stages III and IVa and underwent surgery combined with chemoradiation, and 3 had stage IVb and underwent definitive chemoradiation. Patients who underwent preoperative, postoperative, and definitive chemoradiation received 60, 66, and 70 Gy of radiation, respectively. In all patients receiving concurrent chemoradiation, cisplatin was used, at a dose of 100 mg/m every 3 weeks for 3 cycles. Neoadjuvant chemotherapy included docetaxel, cisplatin, and 5-fluorouracil (TPF) every 3 weeks for 2 to 3 cycles. RESULTS: After a median follow-up of 26 months (16 to 120), a total of 8 patients (44%) have experienced the following: 1 persistent disease (5.5%), 4 local failure (22%), and 3 distant metastases (DM, 16.5%). Five of the 8 patients had preexisting cranial nerve deficits or gross cranial invasion. The 2-, 3-, and 4-year local control (LC), disease-free survival (DFS), and overall survival (OS) were 78%, 72%, and 56%; 75%, 65%, and 52%; and 75%, 50%, and 48%, respectively. Trimodality approach provided 83% LC and 92% DM-free survival, whereas other modalities provided 50% LC and 33% DM-free survival. The causes of death for the entire cohort were DM and local invasion. Acute chemoradiotherapy toxicity was 100% grades 1 and 2 dermatitis, mucositis, and fatigue, 55% developed grades 1 and 2 dysphagia, and 6% had grade 3 mucositis. Long-term toxicity was 28% grade 1 xerostomia, 11% retinopathy and optic neuropathy, and 6% orbital exenteration and grade 3 peripheral neuropathy. CONCLUSIONS: SNUC is an aggressive neoplasm that frequently presents at an advanced stage. Our data show that trimodality approach in the form of surgery combined with chemoradiation seems to offer better LC and lower DM compared with other modalities.

The impact of body mass index on heterotopic ossification.

PURPOSE: To analyze the impact of different body mass index (BMI) as a surrogate marker for heterotopic ossification (HO) in patients who underwent surgical repair (SR) for displaced acetabular fractures (DAF) followed by radiation therapy (RT). METHODS AND MATERIALS: This is a single-institution retrospective study of 395 patients. All patients underwent SR for DAF followed by RT ± indomethacin. All patients received postoperative RT, 7 Gy, within 72 h. The patients were separated into four groups based on their BMI: <18.5, 18.5-24.9, 25-29.9, and >30. The end point of this study was to evaluate the efficacy of RT ± indomethacin in preventing HO in patients with different BMI. RESULTS: Analysis of BMI showed an increasing incidence of HO with increasing BMI: <18.5, (0%) 0/6 patients; 18.5-24.9 (6%), 6 of 105 patients developed HO; 25-29.9 (19%), 22 of 117; >30 (31%), 51 of 167. Chi-square and multivariate logistic regression analysis showed that the correlation between odds of HO and BMI is significant, p < 0.0001. As the BMI increased, the risk of HO and Brooker Classes 3, 4 HO increased. The risk of developing HO is 1.0× (10%) more likely among those with higher BMI compared with those with lower BMI. For a one-unit increase in BMI the log odds of HO increases by 1.0, 95% CI (1.06-1.14). Chi-square test shows no significant difference among all other factors and HO (e.g., indomethacin, race, gender). CONCLUSIONS: Despite similar surgical treatment and prophylactic measures (RT ± indomethacin), the risk of HO appears to significantly increase in patients with higher BMI after DAF. Higher single-fraction doses or multiple fractions and/or combination therapy with nonsteroidal inflammatory drugs may be of greater benefit to these patients.

A prolonged time interval between trauma and prophylactic radiation therapy significantly increases the risk of heterotopic ossification.

PURPOSE: To ascertain whether the time from injury to prophylactic radiation therapy (RT) influences the rate of heterotopic ossification (HO) after operative treatment of displaced acetabular fractures. METHODS AND MATERIALS: This is a single-institution, retrospective analysis of patients referred for RT for the prevention of HO. Between January 2000 and January 2009, 585 patients with displaced acetabular fractures were treated surgically followed by RT for HO prevention. We analyzed the effect of time from injury on prevention of HO by RT. In all patients, 700 cGy was prescribed in a single fraction and delivered within 72 hours postsurgery. The patients were stratified into five groups according to time interval (in days) from the date of their accident to the date of RT: Groups A ≤3, B ≤7, C ≤14, D ≤21, and E >21 days. RESULTS: Of the 585 patients with displaced acetabular fractures treated with RT, (18%) 106 patients developed HO within the irradiated field. The risk of HO after RT increased from 10% for RT delivered ≤3 days to 92% for treatment delivered >21 days after the initial injury. Wilcoxon test showed a significant correlation between the risk of HO and the length of time from injury to RT (p < 0.0001). Chi-square test and multiple logistic regression analysis showed no significant association between all other factors and the risk of HO (race, gender, cause and type of fracture, surgical approach, or the use of indomethacin). CONCLUSIONS: Our data suggest that there is higher incidence and risk of HO if prophylactic RT is significantly delayed after a displaced acetabular fracture. Thus, RT should be administered as early as clinically possible after the trauma. Patients undergoing RT >3 weeks from their displaced acetabular fracture should be informed of the higher risk (>90%) of developing HO despite prophylaxis.