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Aim: To provide a multi-institutional description of current practices of stereotactic body radiotherapy (SBRT) for head and neck cancer., Materials & Methods: 15 international institutions with significant experience in head and neck SBRT were asked to complete a questionnaire covering clinical and technical factors., Results: SBRT is used 10-100% of the time for recurrent primary head and neck cancer, and 0-10% of the time in newly diagnosed disease. Five centers use a constraint for primary disease of 3-5 cm and 25-30 cc. Nine institutions apply a clinical target volume expansion of 1-10 mm and 14 use a planning target volume margin of 1-5 mm. Fractionation regimens vary between 15 and 22 Gy in 1 fraction to 30-50 Gy in 5 or 6 fractions. The risk of carotid blowout quoted in the re-irradiation setting ranges from 3 to 20%., Conclusion: There is considerable heterogeneity in patient selection and techniques in head and neck SBRT practice among experienced centers.

Background: Recent data suggest that intensity-modulated radiation therapy (IMRT) plus brachytherapy boost for unfavorable prostate cancer provides improved biochemical relapse-free survival over IMRT alone. Stereotactic body radiation therapy (SBRT) may be a less invasive alternative to brachytherapy boost. Here, we report the 3-year gastrointestinal (GI) and genitourinary (GU) toxicities of IMRT plus SBRT boost., Materials and Methods: Between March 2008 and September 2012, patients with prostate cancer were treated with robotic SBRT (19.5 Gy in three fractions) followed by fiducial-guided IMRT (45-50.4 Gy) on an institutional protocol. Toxicity was prospectively graded using the common terminology criteria for adverse events version 4.0 (CTCAEv.4) at the start of and at 1- to 6-month intervals after therapy. Rectal telangiectasias were graded using the Vienna Rectoscopy Score (VRS)., Results: At a median follow-up of 4.2 years (2.4-7.5), 108 patients (4 low-, 45 intermediate-, and 59 high-risk) with a median age of 74 years (55-92) were treated with SBRT plus IMRT, with 8% on anticoagulation and an additional 48% on antiplatelet therapy at the start of therapy. The cumulative incidence of late ≥grade 2 GI toxicity was 12%. Of these, 7% were due to late rectal bleeding, with six patients requiring up to two coagulation procedures. One patient with rectal telangiectasias was treated with hyperbaric oxygen (grade 3 toxicity). No rectal fistulas or stenoses were observed. Ten patients had multiple non-confluent telangiectasias (VRS grade 2), and three patients had multiple confluent telangiectasias (VRS grade 3). The cumulative incidence of late grade 3 GU toxicity was 6%. Most late toxicities were due to hematuria requiring bladder fulguration. There were no late ≥grade 4 GU toxicities., Conclusion: Rates of clinically significant GI and GU toxicities are modest following IMRT plus SBRT boost. Future studies should compare cancer control, quality of life, and toxicity with other treatment modalities for patients with high-risk prostate cancer.

Purpose/objectives: Stereotactic body radiation therapy (SBRT) is emerging as a minimally invasive alternative to brachytherapy to deliver highly conformal, dose--escalated radiation therapy (RT) to the prostate. SBRT alone may not adequately cover the tumor extensions outside the prostate commonly seen in unfavorable prostate cancer. External beam radiation therapy (EBRT) with high dose rate brachytherapy boost is a proven effective therapy for unfavorable prostate cancer. This study reports on early prostate-specific antigen and prostate cancer-specific quality of life (QOL) outcomes in a cohort of unfavorable patients treated with intensity-modulated radiation therapy (IMRT) and SBRT boost., Materials/methods: Prostate cancer patients treated with SBRT (19.5 Gy in three fractions) followed by fiducial-guided IMRT (45-50.4 Gy) from March 2008 to September 2012 were included in this retrospective review of prospectively collected data. Biochemical failure was assessed using the Phoenix definition. Patients completed the expanded prostate cancer index composite (EPIC)-26 at baseline, 1 month after the completion of RT, every 3 months for the first year, then every 6 months for a minimum of 2 years., Results: One hundred eight patients (4 low-, 45 intermediate-, and 59 high-risk) with median age of 74 years completed treatment, with median follow-up of 4.4 years. Sixty-four percent of the patients received androgen deprivation therapy prior to the initiation of RT. The 3-year actuarial biochemical control rates were 100 and 89.8% for intermediate- and high-risk patients, respectively. At the initiation of RT, 9 and 5% of men felt their urinary and bowel function was a moderate to big problem, respectively. Mean EPIC urinary and bowel function and bother scores exhibited transient declines, with subsequent return to near baseline. At 2 years posttreatment, 13.7 and 5% of men felt their urinary and bowel function was a moderate to big problem, respectively., Conclusion: At 3-year follow-up, biochemical control was favorable. Acute urinary and bowel symptoms were comparable to conventionally fractionated IMRT and brachytherapy. Patients recovered to near their baseline urinary and bowel function by 2 years posttreatment. A combination of IMRT with SBRT boost is well tolerated with minimal impact on prostate cancer-specific QOL.

Background: The purpose of this study was to report long-term outcomes for a large cohort of patients with head and neck squamous cell carcinoma (HNSCC) who underwent stereotactic body radiotherapy (SBRT) reirradiation., Methods: From 2002 to 2011, 85 patients with previously irradiated HNSCC were treated with SBRT to 94 lesions. Some underwent surgery (29%), and many were treated with induction, concurrent, and/or adjuvant chemotherapy or biologic therapy (70%)., Results: Reirradiation occurred at a median interval from initial radiotherapy (RT) of 32 months. Median follow-up for survivors was 17.3 months. Two-year Kaplan-Meier estimates of overall survival (OS) and locoregional control for patients and lesions treated with curative intent were 24% and 28%, respectively. Interval from initial RT to SBRT of 2 years or more was associated with improved OS (p = .019). Five patients had grade 3 or higher late toxicity (5.9%)., Conclusion: SBRT reirradiation results in limited toxicity. Further research is needed to refine optimal roles for SBRT and intensity-modulated radiotherapy (IMRT) reirradiation., (© 2014 Wiley Periodicals, Inc.)

Background: The optimal treatment for patients with recurrent human papillomavirus (HPV)-positive head and neck cancer is poorly understood., Methods: We investigated treatments and outcomes in patients with recurrent head and neck cancer. Treatments included salvage neck surgery, metastasectomy, hypofractionated reirradiation, chemoembolization, and chemotherapy. Treatment outcomes were compared based on HPV status., Results: A total of 37 patients were identified (12 HPV positive and 25 HPV negative). Demographics were similar. Overall, there was a trend toward a higher number of total treatment interventions in patients with HPV-positive disease (4.5 vs 2.6), but this was statistically insignificant (p=.066). After a mean follow-up of 21 months, median survival in HPV-negative patients was 10.6 months, whereas the median survival had not been reached for HPV-positive patients. Of the 12 HPV-positive patients, 7 were still alive (58%) after a mean follow-up period of 33 months., Conclusion: Multimodality aggressive therapy may improve overall survival in patients with recurrent HPV-positive disease. Further prospective research is warranted., (© 2014 Wiley Periodicals, Inc.)

Introduction: A handful of studies have reported outcomes with CyberKnife radiosurgery (CKRS) for the treatment of trigeminal neuralgia. However, the follow-up has been short with no minimum follow-up required and have included patients with short duration of symptoms. Here we report our institutional experience on patients with a minimum follow-up of 1 year and a median follow-up of 28 months (mean 38.84 months)., Methods: Twenty-five patients with medically and surgically intractable TN received CKRS with a mean marginal radiation dose of 64 Gy applied to an average isodose line of 86% of the affected trigeminal nerve. Follow-up data were obtained by clinical examination and telephone questionnaire. Outcome results were categorized based on the Barrow Neurological Institute (BNI) pain scale with BNI I-III considered to be good outcomes and BNI IV-V considered as treatment failure. BNI facial numbness score was used to assess treatment complications., Results: A large proportion of patients (42.9%) reported pain relief within 1 month following CKRS treatment. The mean time to recurrence of severe pain was 27.8 months (range 1-129 months). At median follow-up of 28 months (mean 38.84 months), actuarial rate of freedom from severe pain (BNI ≥ III) was 72%. At last follow-up 2 (8%) patients had freedom from any pain and no medications (BNI I) and the majority (48%) had some pain that was adequately controlled with medications. Seven patients (28%) had no response to treatment and continued to suffer from severe pain (BNI IV or V). Patient's diabetic status and overall post-treatment BNI facial numbness scores were statistically significant predictors of treatment outcomes., Conclusion: CKRS represents an acceptable salvage option for with medically and/or surgically refractory patients. Even patients with severely debilitating symptoms may experience significant and sustained pain relief after CKRS. Particularly, CKRS remains an attractive option in patients who are not good surgical candidates or possibly even failed surgical therapy. This data should help in setting realistic expectations for weighing the various available treatment options.

Background: Inverted papilloma (IP) of the nasal cavity is a benign tumor that represents 0.5-4% of all nasal tumors and have been known to rarely undergo malignant transformation to squamous carcinoma and even more rarely adenocarcinoma. Synchronous association with low-grade esthesioneuroblastoma (ENB) has been reported in only one case report where a small-sized lesion was treated with surgery alone. Here we report the first case of invasion of IP by high-grade ENB with nodal metastasis that was treated with combined modality therapy., Case Presentation: A case of a 64-year-old African American gentleman presented to the otolaryngology with a 3-month history of recurrent epistaxis. Imaging revealed a large right nasal cavity mass extending into the right sphenoid sinus but without intracranial extension. Surgical pathology revealed high-grade ENB invading IP. An orbitofrontal craniotomy approach was used to achieve complete resection of the mass but with positive margins. Post-operative positron emission tomography/computed tomography showed nodal metastasis. The patient was then treated with adjuvant chemoradiation and remains without evidence of disease at 42 months post-treatment. We discuss the disease presentation, histopathologic features, and disease management with literature support., Conclusion: In this very rare disease presentation where two extremely rare malignancies collide, we show that aggressive management with trimodality therapy of surgery, adjuvant radiation with stereotactic radiosurgical boost, and adjuvant chemotherapy gives excellent results. Given the natural history of the disease, however, long follow-up is needed to declare complete freedom from the disease.

Objective: Effective short-term outcomes have been well documented for trigeminal neuralgia (TN) patients treated with Gamma Knife radiosurgery (GKRS) with reported success rates of 70-90 % with median follow-up intervals of 19-75 months. Fewer series, however, have described uniform long-term follow-up data. In this study, we report our long-term institutional outcomes in patients treated with GKRS after a minimum follow-up of 36 months., Methods: Thirty-six consecutive patients with medically intractable TN received a median radiation dose of 45 Gy applied with a single 4-mm isocenter to the affected trigeminal nerve. Follow-up data were obtained by clinical examination and telephone questionnaire. Outcome results were categorized based on the Barrow Neurological Institute (BNI) pain scale with BNI I-III considered to be good outcomes and BNI IV-V considered as treatment failure. BNI facial numbness score was used to assess treatment complications., Results: The incidence of early pain relief was high (80.5 %) and relief was noted in an average of 1.6 months after treatment. At minimum follow-up of 3 years, 67 % were pain free (BNI I) and 75 % had good treatment outcome. At a mean last follow-up of 69 months, 32 % were free from any pain and 63 % were free from severe pain. Bothersome posttreatment facial numbness was reported in 11 % of the patients. A statistically significant correlation was found between age and recurrence of any pain with age >70 predicting a more favorable outcome after radiosurgery., Conclusion: The success rate of GKRS for treatment of medically intractable TN declines over time with 32 % reporting ideal outcome and 63 % reporting good outcome. Patients older than age 70 are good candidates for radiosurgery. This data should help in setting realistic expectations for weighing the various available treatment options.

Objective: To examine tumor control, hearing preservation, and complication rates after frameless fractionated stereotactic radiosurgery (SRS) in patients with vestibular schwannomas (VS)., Methods: Thirty-seven patients treated with fractionated SRS from 2002 to 2011 were retrospectively analyzed. Ninety-five percent were treated with 25 Gy in five fractions, targeting a median tumor volume of 1.03 cc (range 0.14-7.60)., Results: With a median follow-up of 4.25 years (range, 15 months-9 years), no tumors required an additional treatment resulting in 100% tumor control rate. Radiographic control rate was 91% in 32 patients at a median follow-up of 3 years. Of the 14 patients with serviceable hearing and with audiograms, the hearing preservation rate was 78% at a median follow-up of 18 months. Twenty-six patients with serviceable hearing pretreatment, were evaluated by a phone survey with a hearing preservation rate of 73% at a 5 year median follow-up. There were two cases that developed both new increased trigeminal parasthesias and facial spasms but there were no cases of facial weakness. Patient had 96% of good to excellent satisfaction rate with the treatment at a median follow-up of 5 years., Conclusion: Frameless fractionated SRS treatment of VS results in good rate of tumor control. Hearing preservation rate and rates of cranial nerve toxicity are comparable to what is reported in the literature. Patients choose this modality because of its non-invasive nature and are generally very satisfied with their long term outcome.

The vast majority of glomangiomas are small, benign neoplasms that can occur anywhere in the body but typically arise in the subcutaneous tissues of the extremities and are capable of causing extreme pain. Typically, these lesions are managed surgically with excellent rates of tumor control. On occasion, patients present with a variant of the glomangioma tumor consisting of numerous or recurrent nodules, a condition classified as glomangiomatosis. The authors present a case report of a young patient with multiply recurrent painful glomangiomas of the left foot, who was ultimately diagnosed with glomangiomatosis pedis. After multiple surgeries and surgical consultations, no surgery other than amputation was recommended. Therefore, the patient sought consultation with regard to stereotactic body radiation therapy (SBRT). In the absence of other options, and based on its effectiveness in treating glomus tumors of the head and neck which display similar natural history and histologic features, SBRT was offered. The patient underwent SBRT to the largest of his remaining tumors with excellent local control and significant reduction in pain at two and a half years follow-up.

PURPOSE: The purpose of this study was to review a single-institution experience with the reirradiation of recurrent salivary gland tumors using fractionated stereotactic radiosurgery (SBRT). METHODS: Between 2003 and 2011, 18 patients diagnosed with recurrent, previously irradiated, salivary gland carcinomas were treated with SBRT reirradiation. Median age was 68 for all patients with most tumors being of major salivary gland origin. Most patients did not undergo surgical resection, and among those that did, all had positive margins. Only seven patients received chemotherapy, and the median SBRT dose was 30 Gy given in five fractions with a median cumulative dose of 91.1 Gy. RESULTS: The median overall survival (OS), progression-free survival (PFS), and local control (LRC) were 11.5, 3.5, and 5.5 months, respectively. The 2-year OS, PFS, and LRC rates were 39%, 24%, and 53%, respectively. Statistical analysis identified presence of gross disease and interval to reirradiation as negative predictors of survival outcomes on both univariate and multivariate analyses (p < 0.05). On multivariate analysis, tumor volume was a negative predictor of survival outcomes (p < 0.05). Long-term toxicity analysis revealed four patients in the reirradiated group with soft tissue necrosis, which correlated with the cumulative dose (p = 0.01). CONCLUSION: Our data suggest that SBRT is a reasonable treatment option for reirradiation of salivary gland tumors, but further studies are warranted.

Background: to review a single-institution experience with the management of parotid malignancies treated by fractionated stereotactic body radiosurgery (SBRT)., Findings: Between 2003 and 2011, 13 patients diagnosed with parotid malignancies were treated with adjuvant or definitive SBRT to a median dose of 33 Gy (range 25-40 Gy). There were 11 male and two female patients with a median age of 80. Ten patients declined conventional radiation treatment and three patients had received prior unrelated radiation therapy to neighboring structures with unavailable radiation records. Six patients were treated with definitive intent while seven patients were treated adjuvantly for adverse surgical or pathologic features. Five patients had clinical or pathologic evidence of lymph node disease., Conclusion: at a median follow-up of 14 months only one patient failed locally, and four failed distantly. The actuarial 2-year overall survival, progression-free survival, and local-regional control rates were 46, 84, and 47%, respectively. Statistical analysis revealed surgery as a positive predictor of overall survival while presence of gross disease was a negatively correlated factor (p < 0.05).

This retrospective analysis examines the local control and toxicity of five-fraction fiducial-free CyberKnife stereotactic body radiation therapy (SBRT) for single vertebral body (VB) metastases. All patients had favorable performance status (ECOG 0-1), oligometastatic disease, and no prior spine irradiation. A prescribed dose of 30-35 Gy was delivered in five fractions to the planning target volume (PTV) using the CyberKnife with X-sight spine tracking. Suggested maximum spinal cord and esophagus point doses were 30 and 40 Gy, respectively. A median 30 Gy (IQR, 30-35 Gy) dose was delivered to a median prescription isodose line of 70% (IQR, 65-77%) to 20 patients. At 34 months median follow-up (IQR, 25-40 months) for surviving patients, the 1- and 2-year Kaplan-Meier local control estimates were 80 and 73%, respectively. Two of the five local failures were infield in patients who had received irradiation to the gross tumor volume and three were paravertebral failures just outside the PTV in patients with prior corpectomy. No local failures occurred in patients who completed VB radiation alone. The 1- and 2-year Kaplan-Meier overall survival estimates were 80 and 57%, respectively. Most deaths were attributed to metastatic disease; one death was attributed to local recurrence. The mean maximum point doses were 26.4 Gy (SD, 5.1 Gy) to the spinal cord and 29.1 Gy (SD, 8.9 Gy) to the esophagus. Patients receiving maximum esophagus point doses greater than 35 Gy experienced acute dysphagia (Grade I/II). No spinal cord toxicity was documented. Five-fraction fiducial-free CyberKnife SBRT is an acceptable treatment option for newly diagnosed VB metastases with promising local control rates and minimal toxicity despite the close proximity of such tumors to the spinal cord and esophagus. A prospective study aimed at further enhancing local control by targeting the intact VB and escalating the total dose is planned.

Objective: To report clinical efficacy and toxicity of fractionated CyberKnife radiosurgery for the treatment of hilar lung tumors., Methods: Patients presenting with primary and metastatic hilar lung tumors, treated using the CyberKnife system with Synchrony fiducial tracking technology, were retrospectively reviewed. Hilar location was defined as abutting or invading a mainstem bronchus. Fiducial markers were implanted by conventional bronchoscopy within or adjacent to tumors to serve as targeting references. A prescribed dose of 30 to 40 Gy to the gross tumor volume (GTV) was delivered in 5 fractions. Clinical examination and PET/CT imaging were performed at 3 to 6-month follow-up intervals., Results: Twenty patients were accrued over a 4 year period. Three had primary hilar lung tumors and 17 had hilar lung metastases. The median GTV was 73 cc (range 23-324 cc). The median dose to the GTV was 35 Gy (range, 30 - 40 Gy), delivered in 5 fractions over 5 to 8 days (median, 6 days). The resulting mean maximum point doses delivered to the esophagus and mainstem bronchus were 25 Gy (range, 11 - 39 Gy) and 42 Gy (range, 30 - 49 Gy), respectively. Of the 17 evaluable patients with 3 - 6 month follow-up, 4 patients had a partial response and 13 patients had stable disease. AAT t a median follow-up of 10 months, the 1-year Kaplan-Meier local control and overall survival estimates were 63% and 54%, respectively. Toxicities included one patient experiencing grade II radiation esophagitis and one patient experiencing grade III radiation pneumonitis. One patient with gross endobronchial tumor within the mainstem bronchus developed a bronchial fistula and died after receiving a maximum bronchus dose of 49 Gy., Conclusion: CyberKnife radiosurgery is an effective palliative treatment option for hilar lung tumors, but local control is poor at one year. Maximum point doses to critical structures may be used as a guide for limiting toxicities. Preliminary results suggest that dose escalation alone is unlikely to enhance the therapeutic ratio of hilar lung tumors and novel approaches, such as further defining the patient population or employing the use of radiation sensitizers, should be investigated.

Clinical data suggest that large radiation fractions are biologically superior to smaller fraction sizes in prostate cancer radiotherapy. The CyberKnife is an appealing delivery system for hypofractionated radiosurgery due to its ability to deliver highly conformal radiation and to track and adjust for prostate motion in real-time. We report our early experience using the CyberKnife to deliver a hypofractionated stereotactic body radiation therapy (SBRT) boost to patients with intermediate- to high-risk prostate cancer. Twenty-four patients were treated with hypofractionated SBRT and supplemental external radiation therapy plus or minus androgen deprivation therapy (ADT). Patients were treated with SBRT to a dose of 19.5 Gy in 3 fractions followed by intensity modulated radiation therapy (IMRT) to a dose of 50.4 Gy in 28 fractions. Quality of life data were collected with American Urological Association (AUA) symptom score and Expanded Prostate Cancer Index Composite (EPIC) questionnaires before and after treatment. PSA responses were monitored; acute urinary and rectal toxicities were assessed using Common Toxicity Criteria (CTC) v3. All 24 patients completed the planned treatment with an average follow-up of 9.3 months. For patients who did not receive ADT, the median pre-treatment PSA was 10.6 ng/ml and decreased in all patients to a median of 1.5 ng/ml by 6 months post-treatment. Acute effects associated with treatment included Grade 2 urinary and gastrointestinal toxicity but no patient experienced acute Grade 3 or greater toxicity. AUA and EPIC scores returned to baseline by six months post-treatment. Hypofractionated SBRT combined with IMRT offers radiobiological benefits of a large fraction boost for dose escalation and is a well tolerated treatment option for men with intermediate- to high-risk prostate cancer. Early results are encouraging with biochemical response and acceptable toxicity. These data provide a basis for the design of a phase II clinical trial.

Purpose: Stereotactic radiosurgery (SRS) is an appealing treatment option after previous radiotherapy because of its precision, conformality, and reduced treatment duration. We report our experience with reirradiation using fractionated SRS for head-and-neck cancer., Methods and Materials: From 2002 to 2008, 65 patients received SRS to the oropharynx (n = 13), hypopharynx (n = 8), nasopharynx (n = 7), paranasal sinus (n = 7), neck (n = 7), and other sites (n = 23). Thirty-eight patients were treated definitively and 27 patients with metastatic disease and/or untreated local disease were treated palliatively. Nine patients underwent complete macroscopic resection before SRS. Thirty-three patients received concurrent chemoradiation. The median initial radiation dose was 67 Gy, and the median reirradiation SRS dose was 30 Gy (21-35 Gy) in 2-5 fractions., Results: Median follow-up for surviving patients was 16 months. Fifty-six patients were evaluable for response: 30 (54%) had complete, 15 (27%) had partial, and 11 (20%) had no response. Median overall survival (OS) for all patients was 12 months. For definitively treated patients, the 2-year OS and locoregional control (LRC) rates were 41% and 30%, respectively. Multivariate analysis demonstrated that higher total dose, surgical resection, and nasopharynx site were significantly associated with improved LRC; surgical resection and nonsquamous histology were associated with improved OS. Seven patients (11%) experienced severe reirradiation-related toxicity, including one treatment-attributed death., Conclusion: SRS reirradiation for head-and-neck cancer is feasible. This study demonstrates encouraging response rates with acceptable toxicity. Fractionated SRS reirradiation with concurrent chemotherapy in select patients warrants further study., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objective: Malignant tumors that involve the skull base pose significant challenges to the clinician because of the proximity of critical neurovascular structures and limited effectiveness of surgical resection without major morbidity. The purpose of this study was to evaluate the efficacy and safety of multi-session radiosurgery in patients with malignancies of the skull base., Methods: Clinical and radiographic data for 37 patients treated with image-guided, multi-session radiosurgery between January 2002 and December 2007 were reviewed retrospectively. Lesions were classified according to involvement with the bones of the base of the skull and proximity to the cranial nerves., Results: Our cohort consisted of 37 patients. Six patients with follow-up periods less than four weeks were eliminated from statistical consideration, thus leaving the data from 31 patients to be analyzed. The median follow-up was 37 weeks. Ten patients (32%) were alive at the end of the follow-up period. At last follow-up, or the time of death from systemic disease, tumor regression or stable local disease was observed in 23 lesions, representing an overall tumor control rate of 74%. For the remainder of lesions, the median time to progression was 24 weeks. The median progression-free survival was 230 weeks. The median overall survival was 39 weeks. In the absence of tumor progression, there were no cranial nerve, brainstem or vascular complications referable specifically to CyberKnife radiosurgery., Conclusion: Our experience suggests that multi-session radiosurgery for the treatment of malignant skull base tumors is comparable to other radiosurgical techniques in progression-free survival, local tumor control, and adverse effects.

Background: A randomized phase 3 trial of the treatment of squamous-cell carcinoma of the head and neck compared induction chemotherapy with docetaxel plus cisplatin and fluorouracil (TPF) with cisplatin and fluorouracil (PF), followed by chemoradiotherapy., Methods: We randomly assigned 501 patients (all of whom had stage III or IV disease with no distant metastases and tumors considered to be unresectable or were candidates for organ preservation) to receive either TPF or PF induction chemotherapy, followed by chemoradiotherapy with weekly carboplatin therapy and radiotherapy for 5 days per week. The primary end point was overall survival., Results: With a minimum of 2 years of follow-up (> or =3 years for 69% of patients), significantly more patients survived in the TPF group than in the PF group (hazard ratio for death, 0.70; P=0.006). Estimates of overall survival at 3 years were 62% in the TPF group and 48% in the PF group; the median overall survival was 71 months and 30 months, respectively (P=0.006). There was better locoregional control in the TPF group than in the PF group (P=0.04), but the incidence of distant metastases in the two groups did not differ significantly (P=0.14). Rates of neutropenia and febrile neutropenia were higher in the TPF group; chemotherapy was more frequently delayed because of hematologic adverse events in the PF group., Conclusions: Patients with squamous-cell carcinoma of the head and neck who received docetaxel plus cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy had a significantly longer survival than did patients who received cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy. (ClinicalTrials.gov number, NCT00273546 [ClinicalTrials.gov].)., (Copyright 2007 Massachusetts Medical Society.)

Acinic cell carcinoma is a rare tumor of the head and neck that mainly affects the parotid gland but occasionally involves the minor salivary glands of the upper aerodigestive tract. The authors present a case report of an occurrence of a low-grade acinic cell carcinoma of the true vocal fold, which they believe to be the first reported case of this type of carcinoma in this location. Laryngoscopy and laser excision was completed for what was initially thought to be a granuloma, and pathology confirmed low-grade acinic cell carcinoma of the right true vocal fold. The mass was well circumscribed and did not invade adjacent structures. After complete excision, postoperative radiation therapy was used to reduce local recurrence.

Background: The role of planned neck dissection after organ preservation therapy with radiotherapy or chemotherapy/radiotherapy for advanced head and neck cancers presenting with clinically positive neck disease is still being elucidated. The aim of this study is to review the outcomes of such patients treated by organ preservation therapy at our institution., Methods: A retrospective chart review of 33 patients who underwent planned neck dissections after organ preservation therapy for advanced primary head and neck malignancy. Endpoints measured were disease-free survival and local, regional, and distant control., Setting: Tertiary metropolitan medical center., Results: Two-year actuarial disease-free survival was 61%, and neck control was 92%, with only two failures in the neck. The use of neoadjuvant chemotherapy and total dose of radiotherapy did not correlate with neck control or disease-free survival. The presence of pathologically positive nodal disease at the time of neck dissection did not correlate with recurrent neck disease, but was a predictor of local recurrence (p = .0086)., Conclusions: Our data suggest that for patients undergoing planned neck dissection after organ preservation therapy, neck control is obtained in almost all cases. The presence of pathologically positive nodal disease at the time of surgery may have implications for the incidence of local recurrence.

In order to define technical limitations of conventional external beam irradiation for clinically localized prostate cancer, we evaluated the impact of several reduced-field treatment factors, such as reduced-field (RF) irradiated volume, RF technique, photon energy of treatment, and dose on survival endpoints and local control in a retrospective series. Several survival endpoints, such as disease-specific survival, freedom from relapse survival, biochemical no-evidence of disease (bNED) survival, and local control were associated with several treatment variables using univariate and multivariate analyses in 329 patients. Reduced-field technique appeared to predict survival outcome, with patients treated by bilateral 120 degrees arcs faring less well than those treated by full 360 degrees rotational fields. The irradiated volume of the reduced-field was also significantly associated with survival outcome, with patients treated with smaller volumes faring less well. Local failure rates also appeared increased, although not statistically, in patients treated with smaller RF sizes. In an attempt to explain these detected deficiencies, dose-volume histograms for prostate coverage were created for a small sample of patients. The deficiencies related to small reduced-field volume appeared to be largely attributable to poor dosimetric coverage of the prostate. These results underscore the limitations of conventional external beam treatment for prostate carcinoma when conventional techniques are employed, particularly if small reduced fields are used, and further supports the development of improved treatment techniques, such as conformal irradiation, as alternatives.

Objective: To report the complication rate from planned, posttreatment neck dissections in patients who show control of primary squamous cell carcinoma by chemotherapy and radiotherapy or radiotherapy alone., Design: Retrospective review of case series., Setting: Georgetown University Medical Center, Washington, DC., Patients: Thirty-four patients with clinically positive neck disease treated with organ preservation therapy for squamous cell carcinoma of the head and neck., Interventions: Planned neck dissection after treatment with chemotherapy and radiotherapy or radiotherapy alone., Main Outcome Measure: Perioperative complications., Results: Forty-one neck dissections were performed on 34 patients. Complications were seen in 13 (38%) of 34 patients and 15 (37%) of 41 neck dissections. Wound complications occurred in 9 (22%) of 41 dissections. Neck dissection complication rate did not correlate with previous use of chemotherapy or with the use of brachytherapy at the primary site at the time of the neck dissection. Preoperative radiotherapy dose greater than 70 Gy was associated with complications in 58% vs 29% when preoperative dose was less than 70 Gy (P = .09). This trend was reflected primarily in wound complications (42% vs 14%; P = . 10) and reached significance for skin flap necrosis (33% vs 0%; P = .005). Other factors that were associated with increased complications were preoperative albumin level less than 38 g/L and early neck drain removal., Conclusions: The complication rate associated with planned posttreatment neck dissection is similar to that previously reported for neck dissection. Wound complications are more common when higher preoperative radiotherapy doses are used.

Purpose: We developed and present our experience with high dose rate brachytherapy for treatment of carcinoma of the urethra in medically inoperable women., Materials and Methods: Since 1991, 4 women with localized urethral cancer, medically unable to undergo resection or interstitial implantation, were treated with external beam and high dose rate intracavitary implantation rather than external beam irradiation alone. The fractionated implants were delivered with a high dose rate remote afterloader using a shielded vaginal applicator and modified urethral catheter. The urethral catheter was inserted through the lumen of a 20F Foley tube to improve depth dose. Homogeneous dose distribution was achieved and customized to the individual patient., Results: All high dose rate brachytherapy treatments were given at the clinic without use of sedation or anesthesia. Treatment was well tolerated, and all patients maintained voluntary urinary function and local control at 12 to 55 months after therapy. Chronic morbidity due to urethral, bladder, vaginal or rectal injury, including urethral stenosis, necrosis or fistula, was not noted. Isodose distributions were compared among this technique, interstitial implantation and external beam radiotherapy alone., Conclusions: Although we prefer interstitial implantation as the boost technique for women with urethral cancer, high dose rate brachytherapy is a reasonable option for medically inoperable patients. This outpatient treatment is well tolerated, preserves voluntary urinary function and enhances quality of life.

Purpose: To determine the effects of a lucite beam spoiler on the dose distribution to points inside and outside the primary beam for head and neck irradiation with a 10-MV photon beam., Methods and Materials: Build-up and depth-dose measurements were performed with a parallel-plate ionization chamber for 5 x 5, 10 x 10, and 15 x 15-cm field sizes using lucite spoilers with two different thicknesses at two different lucite-to-skin distances (LSD) for a 10-MV x-ray beam. Corrections were applied to account for finite chamber size. Beam profiles and isodose curves were obtained at several depths using film dosimetry. Beam uniformity was determined from uniformity indices. Peripheral doses (PD) were measured at the surface and at 1.5- and 2.5-cm depths using film dosimetry and a parallel-plate ionization chamber. Measurement points were positioned at the edge of a 10 x 10-cm field and at distances extending to 5.0 cm away. The treatment planning data for the 10-MV x-ray beam were modified to account for the effects of the beam spoiler when treating head and neck patients., Results: The spoiler increased the surface and build-up dose and shifted the depth of maximum dose toward the surface. With a 10-MV x-ray beam and a 1.2-cm-thick lucite at 15 cm LSD, a build-up dose similar to a 6-MV x-ray beam was achieved. The beam uniformity was altered at shallow depths. The peripheral dose was enhanced particularly at the surface and at the points close to the beam edge. The effects of the beam spoiler on beam profile and PD were reduced with increasing depths., Conclusion: The lucite spoiler allowed use of a 10-MV x-ray beam for head and neck treatment by yielding a build-up dose similar to that of a 6-MV x-ray beam while maintaining skin sparing. The increase in PD was at superficial depths and was reduced at points away from the edge; therefore, it is clinically nonsignificant. Spoiling the 10-MV x-ray beam resulted in treatment plans that maintained dose homogeneity without the consequence of increased skin reaction or treatment volume underdose for regions near the skin surface.

Purpose: To determine the dose perturbation effects at the tissue-metal implant interfaces in head and neck cancer patients treated with 6 MV and 10 MV photon beams., Methods and Materials: Phantom measurements were performed to investigate the magnitude of dose perturbation to the tissue adjacent to the titanium alloy implants with (100 mu and 500 mu thick) and without hydroxylapatite (HA) coating. Radiographic and radiochromic films were placed at the upper (and lower) surface of circular metal discs (diameter x thickness: 15 x 3.2, 48 x 3.2, 48 x 3.8 mm2) in a solid water phantom and were exposed perpendicular to radiation beams. The dosimeters were scanned with automatic film scanners. Using a thin-window parallel-plate ion chamber, dose perturbation were measured for a 48 x 3.2 mm2 disc., Results: At the upper surface of the tissue-dental implant interface, the radiographic data indicate that for 15 x 3.2 mm2 uncoated, as well as 100 mu coated discs, dose perturbation is about +22.5% and +20.0% using 6 MV and 10 MV photon beams, respectively. For 48 x 3.2 mm2 discs, these values basically remain the same. However, for 48 x 3.8 mm2 discs, these values increase slightly to about +23.0% and +20.5% for 6 MV and 10 MV beams, respectively. For 48 x 3.2 mm2 discs with 500 mu coating, dose enhancement is slightly lower than that obtained for uncoated and 100 mu coated discs for each beam energy studied. At the lower interface for 15 x 3.2 mm2 and 48 x 3.2 mm2 uncoated and 100 mu coated discs, dose reduction is similar and is about -13.5% and -9.5% for 6 MV and 10 MV beams, respectively. For 48 x 3.8 mm2 discs, dose reduction is about -14.5% and -10.0% for 6 MV and 10 MV beams, respectively. For 48 x 3.2 mm2 discs with 500 mu coating, the dose reduction were slightly higher than those for uncoated and 100 mu coated discs., Conclusions: For the beam energies studied, dose enhancement is slightly larger for the lower energy beam. The results of dose perturbation were similar for 100 mu coated and uncoated discs. These results were slightly lower for the 500 mu coated discs but are not clinically significant. The dosimetry results obtained from radiochromic films were similar to the ones obtained from radiographic film. The dose enhancement results obtained from ion chamber dosimetry are higher than those obtained from film dosimetry. The ion chamber data represent the data at "true" tissue-titanium interface, whereas the ones obtained from film dosimetry represent the data at film-titanium interface.

The use of dental implants can aid in prosthetic rehabilitation of patients after ablative cancer surgery of the oral cavity. Biological effects of radiation therapy and the enhancement of radiation by metal implants have limited the use of dental implants. This article presents a case of dental implants used prior to radiation therapy for rehabilitation of a mandibulectomy patient and discusses the current understanding of radiation effects on bone and metal implants.

Purpose: To determine the perturbation effect in the surface layers of lesions located in the air-tumor tissue interface of larynx using 60Co, 6 MV, and 10 MV photon beams., Methods and Materials: Thermoluminescent dosimeters (TLDs), were embedded at 16 measurement locations in slab no. 8 of a humanoid phantom and exposed to two lateral-opposed beams using standard small 7 x 7 cm fields. Similarly, radiographic and radiochromic films were placed between slabs no. 7 and no. 8 of the humanoid phantom and exposed to two lateral-opposed radiation beams. The dosimeters were irradiated with 60Co, 6 MV, and 10 MV photon beams. Computer tomography (CT) treatment planning without inhomogeneity correction was performed., Results: At the tissue-air interface, the average measured percentage dose (% dosem) is about (108.7 +/- 4.8)% with TLD data, (96.8 +/- 2.5)% with radiographic film data, and (100.8 +/- 4.9)% with radiochromic film data. Similarly, in the central part of the cavity, the % dosem is (98.4 +/- 3.1)% with TLD data, (94.3 +/- 3.3)% with radiographic film data, and (91.7 +/- 5.0)% with radiochromic film data. Using the CT-based generated dose distribution (without inhomogeneity correction), the average calculated percentage dose (% dosec) is (98.7 +/- 1.0)% at the tissue-air interface and 98% in the central part of the air cavity., Conclusion: For the beam energies studied, the variation from the % dosem at the tissue-air interface for a given dosimetry technique is relatively small [< 5% (TLD), < 3% (radiographic), and < 5% (radiochromic)] and therefore should not be significant in clinical settings. The variation from the % dosem at the tissue-air interface is more significant for lower energies [8% (60Co), 7.3% (6 MV)]. This variation is about 4.3% for 10 MV photon beam, therefore, while our institutional practice favors lower energy (60Co to 6 MV) for node-negative glottic cancers, physical/dosimetric evidence offers no disadvantage to the use of higher energy photons.

Background: Resection of liver metastases from colorectal carcinoma can be curative. Unresectable but liver-confined metastases might be ablated by high-dose radiation with a similar curative result., Methods: At Georgetown University Hospital, 22 patients with unresectable hepatic metastases from colorectal carcinoma underwent 24 interstitial irradiation procedures at laparotomy in a Phase I-II study. A single dose was administered with a high-dose rate iridium-192 afterloader. Dose to the tumor periphery was 20 Gy, 25 Gy, and 30 Gy in 13, 9, and 2 procedures, respectively., Results: No acute or chronic radiation toxicity has occurred at a median follow-up of 11 months. Median actuarial local control at irradiated sites was 8 months, with 26% actuarial local control at 26 months by computed tomography (CT) or magnetic resonance imaging (MRI) scanning. In the two patients undergoing two procedures each, a second biopsy of previously irradiated areas demonstrated tumor eradication., Conclusions: This innovative, radical approach to unresectable colorectal hepatic metastases proved safe. Additional study is needed to determine whether interstitial irradiation is as effective as surgical resection, or whether it alters the natural history of the disease or longevity.

A prospective randomized study investigating the effectiveness of adjuvant local graft irradiation (LGI) following renal transplantation was performed at Georgetown University Hospital from 1983 until 1988. One hundred and thirty-eight patients were enrolled in the study with 117 patients receiving cadaver kidney transplantations and 21 patients receiving living related kidney transplantations. Seventy-one patients were randomized to receive adjuvant local graft irradiation consisting of 600 cGy in four fractions with chemical immunosuppression whereas the remaining 67 patients received chemical immunosuppression only (control group). The two groups were comparable at entry with respect to potentially important prognostic variables. Median follow-up for all patients was 30 months. The 3-year actuarial allograft success rate was 75% and 68% for the local graft irradiation and control groups, respectively. A nonsignificant trend favoring the irradiated group was noted. Subgroup analysis of the 21 recipients of kidneys from living related donors suggested an improvement in allograft survival for the local graft irradiation arm. Cadaver allograft survival was not significantly different between the two treatment arms. There was no apparent benefit in kidney function or time to the first rejection episode in the group receiving local graft irradiation.

Surgical resection of hepatic metastases offers long-term survival, and possible cure, for selected patients with colorectal carcinoma. Fifty percent of patients considered candidates for resection are found to have disease confined to the liver. The resections necessary are often more extensive than predicted preoperatively, which provides an opportunity for innovative approaches using radiation therapy. The intraoperative radiation therapy technique presented here offers the ability to control multiple metastatic deposits in patients not deemed resectable. This is achieved using remote afterloading interstitial (Ir-192) radiation therapy to deliver tumoricidal radiation doses to limited volumes within the liver. The technique was used to treat 11 patients in a pilot study, delivering radiation doses of 20 Gy to the periphery of predetermined target volumes in a single treatment. The number of metastatic deposits treated ranged from 2 to 11 separate tumors with maximum diameters from 3 to 9 cm (median 6 cm). Hospitalizations were from 6 to 23 days (median 8) with only one patient experiencing a surgically related complication (wound dehiscence and pneumonia). There were no radiation related complications on follow-up to 18 months. Biopsies of two treated sites in a patient undergoing reoperation confirmed control of tumors by this procedure. This technique is offered as a standby procedure to patients undergoing exploration for hepatic resection at our institution.

Perhexiline maleate (Pexid), a promising clinical antiarrhythmic and antianginal drug, was evaluated for its electrophysiologic effects on the entire conduction system of the intact canine heart throughout a wide range of therapeutic and potentially toxic doses. Intracardiac conduction times were measured by bipolar intramyocardial and transvenous endocardial electrodes before and following the intravenous administration of each dose of perhexiline maleate, 3 mg/kg every 30 min for a total of 4 doses in 7 open-chest anesthetized dogs. Eight animals served as controls in which similar operative technique and electrophysiologic variables were recorded after infusion of the maleate diluent. In addition, the effects of perhexiline on atrial and ventricular thresholds to electrical stimulation were recorded, as well as the QRS and QT intervals, sinus rate, and rhythm disorders. It was observed that perhexiline did not significantly (p greater than .05) alter sinus rate, QT interval, QRS duration, PR interval, intra-atrial conduction time, atrioventricular nodal conduction time, and His-Purkinje conduction velocity. The drug did not affect the cardiac threshold to electrical stimulation of less than 0.1 ma. No ectopic atrial or ventricular activity emerged during the accumulated influence of the agent. From this study, it is concluded that perhexiline does not exert deleterious actions on the conduction system of the intact canine heart. In view of the negligible toxic effects and its efficacy in treating ventricular tachyarrhythmias in patients, the drug deserves further clinical evaluation.

Fourteen patients with a history of colonic cancer were evaluated for metastatic disease and were thought to have unresectable disease confined to the liver. Exploratory surgery revealed that two patients had extensive extrahepatic disease, and the procedure was terminated. In 12 patients, closed-end needles (diameter, 2.1 mm) were introduced into each nodule and connected to a 370-MBq (10-Ci) afterloading iridium source. Radiation doses were dependent on nodule size, providing minimum doses of 20 Gy (2000 rad) to the lesion's periphery with rapid radiation falloff avoiding toxic effects to adjacent normal tissue. The maximum number of nodules treated in one patient was 11. The largest nodule treated measured 9 x 6.5 x 6 cm. Cholecystectomy in four patients allowed precise implantation and obviated biliary fistula. Preoperative computed tomography underestimated the number of hepatic metastases in all cases but one, and treatment-induced computed tomographic alterations further limited its utility. Radiation treatment was well tolerated, and the median hospitalization was eight days. Of ten patients whose preoperative carcinoembryonic antigen values exceeded 10 ng/dL, the values in six patients decreased postoperatively.

Liver metastases from colorectal carcinomas occur frequently. While surgical resection offers the only hope for long-term cure, unsuspected bilobar metastases or extrahepatic metastatic disease may be found at laparotomy, precluding hepatic resection for cure. In this setting intraoperative interstitial hepatic irradiation using the Gamma Med II (Mick Radio-Nuclear Instruments, Bronx, New York) remote afterloading irradiator and an Iridium-192 source permits delivery of a tumoricidal dose to liver tumor(s) with a limited radiation dose to adjacent normal liver. Six patients underwent laparotomy for potential resection of hepatic metastases in a shielded operating room equipped with remote anesthesia monitoring capability and were found to be unresectable. An upper hand retractor facilitated liver exposure during the exploratory and subsequent radiation phases of the procedure. Intraoperative interstitial radiation therapy was performed in each patient. No significant complications occurred on follow-up from 2 to 9 months. Hepatic tumor regression or stabilization occurred on sonography and/or CT scan in each case with a median follow-up of 5 months. The technique offers the potential to ablate discrete tumor nodules within the liver. Ongoing clinical trials will determine the role of intraoperative interstitial radiation in the treatment of hepatic metastases.

A new technique is reported for the treatment of hepatic metastases using sonography-directed percutaneous placement of a 14-gauge needle applicator and a high-intensity "remote afterloading" iridium-192 (Ir-192) source for interstitial radiation therapy. The results with six patients show that the procedure is easily performed, patient tolerance is good, and there is minimal disruption of the patient's lifestyle. Hospitalizations have been less than 24 hr. Partial response or stable disease in the liver was observed in all six patients. Tumoricidal doses up to 5000 rad (cGy) in a single treatment with durations from 7 to 41 min were achieved in small volumes (less than 25 cm3) with no clinically significant toxicity on follow-up evaluations from 2-6 months. The technique appears to ablate discrete metastatic tumor deposits in the liver.

Current treatment of pancreatic carcinoma is not adequate. Local recurrence and distant metastases result in disease progression and death in the majority of patients. The authors focus on the natural history of the disease, the results with currently available treatments and the future of combined modality treatment. Reviewing the literature in support of combined treatments, they observe that several potential benefits may result: Palliation of symptoms, prolongation of survival (albeit measured in months), and occasional long-term survival. Patients with carcinoma of the pancreas are appropriate candidates for investigational treatment protocols.