30-day morbidity and mortality after transoral robotic surgery for human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma: A retrospective analysis of two prospective adjuvant de-escalation trials (MC1273 & MC1675).

OBJECTIVE: Dose de-escalation of adjuvant therapy (DART) in patients with HPV(+)OPSCC was investigated in two prospective Phase II and III clinical trials (MC1273 and MC1675). We report the 30-day morbidity and mortality associated with primary TORS resection in patients enrolled in these trials. MATERIALS AND METHODS: Patients with HPV(+)OPSCC, who underwent TORS resection between 2013 and 2020 were considered in this analysis. The severity of postoperative transoral bleeding was graded using both the Hinni Grade (HG) transoral surgery bleeding scale and the Common Terminology for Adverse Events (CTCAE) v5.0. Post-surgical complications within 30 days of surgery, as well as rates of tracheostomy, PEG and nasogastric tube placement. RESULTS: 219 patients were included. A total of 7 (3.2 %) patients had a tracheostomy placed at the time of surgery, and all were decannulated within 26 days (median: 5, range: 2-26). There were 33 (15.1 %) returns to the emergency department (ED) with 10 (4.6 %) patients requiring readmission. Using the HG scale, 10 (4.6 %) patients experienced ≥ Grade 3 bleeding with no Grade 5 or 6 bleeds. In contrast, using the CTCAE scale, 15 patients (6.8 %) experienced ≥ Grade 3 bleeding with no Grade 5 bleeds. There was one post-operative death in a patient withdrawn from the trial, and no deaths related to hemorrhage. CONCLUSION AND RELEVANCE: TORS for HPV(+)OPSCC in carefully selected patients at a high volume center was associated with low morbidity and mortality.

Scalable radiotherapy data curation infrastructure for deep-learning based autosegmentation of organs-at-risk: A case study in head and neck cancer.

In this era of patient-centered, outcomes-driven and adaptive radiotherapy, deep learning is now being successfully applied to tackle imaging-related workflow bottlenecks such as autosegmentation and dose planning. These applications typically require supervised learning approaches enabled by relatively large, curated radiotherapy datasets which are highly reflective of the contemporary standard of care. However, little has been previously published describing technical infrastructure, recommendations, methods or standards for radiotherapy dataset curation in a holistic fashion. Our radiation oncology department has recently embarked on a large-scale project in partnership with an external partner to develop deep-learning-based tools to assist with our radiotherapy workflow, beginning with autosegmentation of organs-at-risk. This project will require thousands of carefully curated radiotherapy datasets comprising all body sites we routinely treat with radiotherapy. Given such a large project scope, we have approached the need for dataset curation rigorously, with an aim towards building infrastructure that is compatible with efficiency, automation and scalability. Focusing on our first use-case pertaining to head and neck cancer, we describe our developed infrastructure and novel methods applied to radiotherapy dataset curation, inclusive of personnel and workflow organization, dataset selection, expert organ-at-risk segmentation, quality assurance, patient de-identification, data archival and transfer. Over the course of approximately 13 months, our expert multidisciplinary team generated 490 curated head and neck radiotherapy datasets. This task required approximately 6000 human-expert hours in total (not including planning and infrastructure development time). This infrastructure continues to evolve and will support ongoing and future project efforts.

Randomized trial addressing risk features and time factors of surgery plus radiotherapy in advanced head-and-neck cancer.

PURPOSE: A multi-institutional, prospective, randomized trial was undertaken in patients with advanced head-and-neck squamous cell carcinoma to address (1) the validity of using pathologic risk features, established from a previous study, to determine the need for, and dose of, postoperative radiotherapy (PORT); (2) the impact of accelerating PORT using a concomitant boost schedule; and (3) the importance of the overall combined treatment duration on the treatment outcome. METHODS AND MATERIALS: Of 288 consecutive patients with advanced disease registered preoperatively, 213 fulfilled the trial criteria and went on to receive therapy predicated on a set of pathologic risk features: no PORT for the low-risk group (n = 31); 57.6 Gy during 6.5 weeks for the intermediate-risk group (n = 31); and, by random assignment, 63 Gy during 5 weeks (n = 76) or 7 weeks (n = 75) for the high-risk group. Patients were irradiated with standard techniques appropriate to the site of disease and likely areas of spread. The study end points were locoregional control (LRC), survival, and morbidity. RESULTS: Patients with low or intermediate risks had significantly higher LRC and survival rates than those with high-risk features (p = 0.003 and p = 0.0001, respectively), despite receiving no PORT or lower dose PORT, respectively. For high-risk patients, a trend toward higher LRC and survival rates was noted when PORT was delivered in 5 rather than 7 weeks. A prolonged interval between surgery and PORT in the 7-week schedule was associated with significantly lower LRC (p = 0.03) and survival (p = 0.01) rates. Consequently, the cumulative duration of combined therapy had a significant impact on the LRC (p = 0.005) and survival (p = 0.03) rates. A 2-week reduction in the PORT duration by using the concomitant boost technique did not increase the late treatment toxicity. CONCLUSIONS: This Phase III trial established the power of risk assessment using pathologic features in determining the need for, and dose of, PORT in patients with advanced head-and-neck squamous cell cancer in a prospective, multi-institutional setting. It also revealed the impact of the overall treatment time in the combination of surgery and PORT on the outcome in high-risk patients and showed that PORT acceleration without a reduction in dose by a concomitant boost regimen did not increase the late complication rate. These findings emphasize the importance of coordinated interdisciplinary care in the delivery of combined surgery and RT.

Does increased nerve length within the treatment volume improve trigeminal neuralgia radiosurgery? A prospective double-blind, randomized study.

PURPOSE: To test the hypothesis that increasing the nerve length within the treatment volume for trigeminal neuralgia radiosurgery would improve pain relief. METHODS AND MATERIALS: Eighty-seven patients with typical trigeminal neuralgia were randomized to undergo retrogasserian gamma knife radiosurgery (75 Gy maximal dose with 4-mm diameter collimators) using either one (n = 44) or two (n = 43) isocenters. The median follow-up was 26 months (range 1-36). RESULTS: Pain relief was complete in 57 patients (45 without medication and 12 with low-dose medication), partial in 15, and minimal in another 15 patients. The actuarial rate of obtaining complete pain relief (with or without medication) was 67.7% +/- 5.1%. The pain relief was identical for one- and two-isocenter radiosurgery. Pain relapsed in 30 of 72 responding patients. Facial numbness and mild and severe paresthesias developed in 8, 5, and 1 two-isocenter patients vs. 3, 4, and 0 one-isocenter patients, respectively (p = 0.23). Improved pain relief correlated with younger age (p = 0.025) and fewer prior procedures (p = 0.039) and complications (numbness or paresthesias) correlated with the nerve length irradiated (p = 0.018). CONCLUSIONS: Increasing the treatment volume to include a longer nerve length for trigeminal neuralgia radiosurgery does not significantly improve pain relief but may increase complications.

External-beam radiation therapy in the treatment of diffuse tracheobronchial amyloidosis.

Tracheobronchial amyloidosis is characterized by deposits of amyloid in airway walls. No effective treatment is known. We describe a 59-year-old woman who presented with increasing symptoms of airway obstruction due to diffuse deposition of amyloid throughout her tracheobronchial tree. She was treated with external-beam radiation therapy (20 Gy) with marked improvement in her symptoms, effort tolerance, bronchoscopic appearance, and forced expiratory volume in 1 second (1.39 L to 1.97 L [42%]). This improvement was maintained during 21 months of follow-up.

High-dose trigeminal neuralgia radiosurgery associated with increased risk of trigeminal nerve dysfunction.

OBJECTIVE: Stereotactic radiosurgery is being used with more frequency in the management of patients with trigeminal neuralgia. To improve facial pain outcomes, many centers have increased the prescribed radiation dose to the trigeminal nerve. METHODS: Between April 1997 and December 1999, 68 patients underwent radiosurgery for trigeminal neuralgia with use of the Leksell gamma knife (Elekta Instruments, Norcross, GA) and a single 4-mm isocenter of radiation. Twenty-seven patients (40%) received 70 Gy (low dose) of irradiation and 41 patients (60%) received 90 Gy (high dose). The groups were similar with regard to age, sex, duration of pain, number of prior surgeries, and preexisting trigeminal deficits. The primary facial pain outcomes for analysis were excellent (pain-free, no medications) and good (pain-free, reduced medications). The mean length of follow-up after radiosurgery was 14.4 months (range, 2-36 mo). RESULTS: At last follow-up examination, 11 (41%) of the 27 patients with low-dose radiosurgery remained pain-free compared with 25 (61%) of the 41 patients with high-dose radiosurgery (P = 0.17). Additional surgery was performed in 12 low-dose patients (44%) and 8 high-dose patients (20%) (P = 0.05). High-dose radiosurgery was associated with an increased rate of permanent trigeminal nerve dysfunction (54% versus 15%, P = 0.003). Bothersome dysesthesias occurred in 13 high-dose patients (32%), whereas only 1 low-dose patient had this complication (P = 0.01). Three high-dose patients (8%) developed corneal numbness after radiosurgery. Pain recurred with more frequency in patients not developing trigeminal nerve dysfunction after radiosurgery (9 of 22 patients, 41 %) compared with those who sustained facial numbness, paresthesias, or dysesthesias (4 of 27 patients, 15%); however, the difference was not statistically significant (P = 0.08). CONCLUSION: Higher doses of radiation may correlate with better facial pain outcomes after radiosurgery for trigeminal neuralgia. However, the incidence of significant trigeminal nerve dysfunction is markedly increased after radiosurgery for patients receiving high-dose radiosurgery. Because of the nonselective nature of this ablative technique, dose prescription should be limited to less than 90 Gy.

Results of combined stereotactic radiosurgery and transarterial embolization for dural arteriovenous fistulas of the transverse and sigmoid sinuses.

OBJECT: Most dural arteriovenous fistulas (DAVFs) of the transverse and sigmoid sinuses do not have angiographically demonstrated features associated with intracranial hemorrhage and, therefore, may be treated nonsurgically. The authors report their experience using a staged combination of radiosurgery and transarterial embolization for treating DAVFs involving the transverse and sigmoid sinuses. METHODS: Between 1991 and 1998, 25 patients with DAVFs of the transverse and/or sigmoid sinuses were treated using stereotactic radiosurgery; 22 of these patients also underwent transarterial embolization. Two patients were lost to follow-up review. Clinical data, angiographic findings, and follow-up records for the remaining 23 patients were collected prospectively. The mean duration of clinical follow up after radiosurgery was 50 months (range 20-99 months). The 18 women and five men included in this series had a mean age of 57 years (range 33-79 years). Twenty-two (96%) of 23 patients presented with pulsatile tinnitus as the primary symptom; two patients had experienced an earlier intracerebral hemorrhage (ICH). Cognard classifications of the DAVFs included the following: I in 12 patients (52%), IIa in seven patients (30%), and III in four patients (17%). After treatment, symptoms resolved (20 patients) or improved significantly (two patients) in 96% of patients. One patient was clinically unchanged. No patient sustained an ICH or irradiation-related complication during the follow-up period. Seventeen patients underwent follow-up angiographic studies at a mean of 21 months after radiosurgery (range 11-38 months). Total or near-total obliteration (> 90%) was seen in 11 patients (65%), and more than a 50% reduction in six patients (35%). Two patients experienced recurrent tinnitus and underwent repeated radiosurgery and embolization at 21 and 38 months, respectively, after the first procedure. CONCLUSIONS: A staged combination of radiosurgery and transarterial embolization provides excellent symptom relief and a good angiographically verified cure rate for patients harboring low-risk DAVFs of the transverse and sigmoid sinuses. This combined approach is a safe and effective treatment strategy for patients without angiographically determined risk factors for hemorrhage and for elderly patients with significant comorbidities.

Long-term results of a phase I/II study of high-dose thoracic radiotherapy with concomitant cisplatin and etoposide in limited stage small-cell lung cancer.

This report presents the results from a Mayo Clinic initiated phase I/II study exploring a potentially more aggressive local and systemic approach for treatment of limited-stage small-cell lung cancer (LSSCLC). Five patients with LSSCLC received three cycles of induction cyclophosphamide, etoposide, and infusion cisplatin chemotherapy. This was followed by accelerated hyperfractionated thoracic radiotherapy (AHFTRT) consisting of 30 Gy given as 1.5-Gy fractions twice daily with a 2-week break and then the AHFTRT was repeated. The AHFTRT was given concomitantly with daily oral etoposide and daily intravenous cisplatin. Prophylactic cranial radiation was delivered with the AHFTRT. After completion of the AHFTRT, patients received 4 cycles of oral etoposide maintenance chemotherapy. Follow-up of patients was continued until death or a minimum of 42 months. Three patients had severe toxic responses. No patients completed the entire protocol because of toxicity or progression during treatment. Three patients completed the majority of the protocol except for the four cycles of maintenance etoposide. Four of five patients achieved a complete response. There were two recurrences within the irradiated field, and distant metastases developed in four patients. Acute nonlymphocytic leukemia developed in one patient, who died 2 months later. No patient completed the entire protocol, because of toxicity or progression; therefore, this protocol cannot be recommended for the treatment of LSSCLC.

Meningioma radiosurgery: tumor control, outcomes, and complications among 190 consecutive patients.

OBJECTIVE: To determine local control (LC) and complication rates for patients with intracranial meningiomas who underwent radiosurgery. METHODS: One hundred ninety consecutive patients with 206 meningiomas underwent radiosurgery between 1990 and 1998. One hundred forty-seven tumors (77%) involved the cranial base. The median age at the time of radiosurgery was 58 years (range, 20-90 yr). There were 126 female patients (66%). One hundred twelve patients (59%) had undergone one or more previous operations (median, 1; range, 1-5). Twenty-two patients (12%) had either atypical (n = 13) or malignant (n = 9) tumors. The median prescription isodose volume was 8.2 cm(3) (range, 0.5-50.5 cm(3)), and the median tumor margin dose was 16 Gy (range, 12-36 Gy). The median imaging and clinical follow-up periods were 40 and 47 months, respectively. RESULTS: Overall survival rates for the entire cohort at 5 and 7 years were 82 and 82%, respectively; cause-specific survival rates at 5 and 7 years were 94 and 92%, respectively. The cause-specific survival rates at 5 years for patients with benign, atypical, and malignant tumors were 100, 76, and 0%, respectively (P < 0.0001). The 5-year LC rate was 89%, with 114 tumors (56%) decreasing in size. LC rates were correlated with tumor histological features (P < 0.0001); patients with benign tumors exhibited a 5-year LC rate of 93%, compared with 68 and 0% for patients with atypical or malignant meningiomas, respectively. No correlation was observed between radiation dose and LC rate. Twenty-four patients (13%) experienced treatment-related complications, including cranial nerve deficits (8%), symptomatic parenchymal changes (3%), internal carotid artery stenosis (1%), and symptomatic cyst formation (1%). Only six patients (3%) exhibited decreases in functional status that were directly related to radiosurgery. Tumor volume, tumor margin dose, or previous radiotherapy was not associated with the development of radiation-related complications. CONCLUSION: Radiosurgery is an effective management strategy for many patients with meningiomas. Patients with atypical or malignant tumors exhibit high recurrence rates despite the use of radiosurgery, and these patients continue to exhibit worse cause-specific survival rates despite aggressive treatment, including surgery, external-beam radiotherapy, and radiosurgery. Further study is needed to determine the tumor control and complication rates 10 years or more after meningioma radiosurgery.

Stereotactic radiosurgery for cavernous malformations.

OBJECT: The use of stereotactic radiosurgery to treat cerebral cavernous malformations (CMs) is controversial. To evaluate the efficacy and safety of CM radiosurgery, the authors reviewed the experience at the Mayo Clinic during the past 10 years. METHODS: Seventeen patients underwent radiosurgery for high-surgical-risk CMs in the following sites: thalamus/basal ganglia (four patients), brainstem (12 patients), and corpus callosum (one patient). All patients had experienced at least two documented hemorrhages before undergoing radiosurgery. Stereotactic magnetic resonance (MR) imaging was used for target localization in all cases. The median margin radiation dose was 18 Gy and the median maximum dose was 32 Gy. The median length of follow-up review following radiosurgery was 51 months. The annual hemorrhage rate during the 51 months preceding radiosurgery was 40.1%, compared with 8.8% in the first 2 years following radiosurgery and 2.9% thereafter. In 10 patients (59%) new neurological deficits developed that were associated with regions of increased signal on long-repetition time MR imaging performed a median of 8 months (range 5-16 months) after radiosurgery. Three patients recovered, giving the group a permanent radiation-related morbidity rate of 41%. Compared with 31 patients harboring arteriovenous malformations (AVMs) of sizes and in locations similar to those of the aforementioned CMs, who underwent radiosurgery during the same time period, the patients with CMs were more likely to experience radiation-related complications (any complication, 59% compared with 10%; p < 0.001; permanent complication, 41% compared with 10%; p = 0.02). CONCLUSIONS: It is impossible to conclude that radiosurgery protects patients with CMs against future hemorrhage risk based on the available data, although it appears that some reduction in the bleeding rate occurs after a latency interval of several years. The risk of radiation-related complications after radiosurgery to treat CMs is greater than that found after radiosurgery in AVMs, even when adjusting for lesion size and location and for radiation dose.

Decreasing the dosimetric effects of misalignment when using a mono-isocentric technique for irradiation of head and neck cancer.

PURPOSE: The purpose of this study was to quantify and develop methods to decrease inhomogeneities created with field edge mismatch when using a mono-isocentric beam-split technique. METHODS AND MATERIALS: We validated techniques to determine dose across a half-blocked field edge and quantified potential sources of systematic matchline error. Then, two methods were used to evaluate matchline doses. The first used film dosimetry data from a half-beam field and a spreadsheet. Duplication and reversal provided two columns, each representing a beam-split field edge. Summation simulated perfect abutment and shifting created various gaps and overlaps. The second method involved obtaining dose profiles at midfield along the ray perpendicular to abutted, overlapped, and gapped beam-split fields on six linear accelerators. To enlarge the penumbra, we designed several field edge modifiers, then re-evaluated matchline doses. The field edge modifiers applicability to a 3-field head and neck treatment technique was also examined. RESULTS: Film-determined dose profiles provide similar information across a beam-split field edge as an ionization chamber. With the mono-isocentric beam-split technique, a 4-mm overlap or gap produces inhomogeneities nearly 60% above or below the intended dose. A 2-mm overlap or gap produces inhomogeneities nearly 30% above or below the intended dose. A customized penumbra generator decreased the magnitude of these inhomogeneities to 20% and 10%, respectively. CONCLUSION: The two methods of evaluating matchline dose described above gave similar results. When using the mono-isocentric half-field technique, small misalignments produce worrisome regions of inhomogeneity. Our penumbra generator substantially decreases the magnitude of the dose inhomogeneities, although the volume receiving an inhomogeneous dose increases.

An analysis of facial nerve function in irradiated and unirradiated facial nerve grafts.

PURPOSE: The effect of high-dose radiation therapy on facial nerve grafts is controversial. Some authors believe radiotherapy is so detrimental to the outcome of facial nerve graft function that dynamic or static slings should be performed instead of facial nerve grafts in all patients who are to receive postoperative radiation therapy. Unfortunately, the facial function achieved with dynamic and static slings is almost always inferior to that after facial nerve grafts. In this retrospective study, we compared facial nerve function in irradiated and unirradiated nerve grafts. METHODS AND MATERIALS The medical records of 818 patients with neoplasms involving the parotid gland who received treatment between 1974 and 1997 were reviewed, of whom 66 underwent facial nerve grafting. Fourteen patients who died or had a recurrence less than a year after their facial nerve graft were excluded. The median follow-up for the remaining 52 patients was 10.6 years. Cable nerve grafts were performed in 50 patients and direct anastomoses of the facial nerve in two. Facial nerve function was scored by means of the House-Brackmann (H-B) facial grading system. Twenty-eight of the 52 patients received postoperative radiotherapy. The median time from nerve grafting to start of radiotherapy was 5.1 weeks. The median and mean doses of radiation were 6000 and 6033 cGy, respectively, for the irradiated grafts. One patient received preoperative radiotherapy to a total dose of 5000 cGy in 25 fractions and underwent surgery 1 month after the completion of radiotherapy. This patient was placed, by convention, in the irradiated facial nerve graft cohort. RESULTS: Potential prognostic factors for facial nerve function such as age, gender, extent of surgery at the time of nerve grafting, preoperative facial nerve palsy, duration of preoperative palsy if present, or number of previous operations in the parotid bed were relatively well balanced between irradiated and unirradiated patients. However, the irradiated graft group had a greater proportion of patients with pathologic evidence of nerve invasion (p = 0.007) and unfavorable type of nerve graft (p = 0.04). Although the irradiated graft cohort had more potentially negative prognostic factors, there was no difference in functional outcome (H-B Grade III or IV) between irradiated and unirradiated graft patients. H-B Grades III, IV, V, and VI were the best postoperative facial nerve functions achieved in 35%, 39%, 13%, and 13% of patients, respectively. The patient with preoperative radiotherapy never recovered any facial nerve function (H-B Grade VI). Median time to best facial nerve function after surgery was longer in the irradiated patients (13.1 vs. 10.8 months), but this was not statistically significant (p = 0.10). Presence of preoperative facial nerve palsy (p = 0.005), duration of preoperative palsy (p = 0.003), and age greater than 60 years at the time of grafting (p = 0. 04) were all negative prognostic factors for achieving a functional facial nerve on univariate analysis. Analysis of age as a continuous variable (p = 0.12) and pathologic evidence of nerve invasion (p = 0. 1) revealed a trend toward negative prognostic factors. Gender, number of previous operations in the parotid bed, extent of surgery at the time of nerve grafting, and type of grafting procedure were not significant prognostic factors. Whether radiotherapy was delivered less than 6 weeks after nerve grafting or more than 6 weeks had no impact on achievement of a functional facial nerve. CONCLUSION: Negative prognostic factors for achieving a functional facial nerve in our series include the presence of preoperative facial nerve palsy, duration of preoperative palsy, and age greater than 60 years. Radiotherapy was not a negative prognostic factor. Comparing irradiated and unirradiated grafts revealed no difference in best facial nerve function achieved, despite the presence of a greater proportion of negative prognostic factors in

The rationale and technique of staged-volume arteriovenous malformation radiosurgery.

PURPOSE: Stereotactic radiosurgery is an effective management strategy for properly selected arteriovenous malformation (AVM) patients. However, the risk of postradiosurgical radiation-related injury generally limits this procedure to patients with AVMs of an average diameter of 3 cm or less. Radiosurgery of large AVMs in a planned staged fashion was undertaken to limit the radiation exposure to the surrounding normal brain. METHODS AND MATERIALS: Between April 1997 and December 1999, 10 patients with a median AVM volume of 17.4 cm(3) (range, 7.4-53.3 cm(3)) underwent staged-volume radiosurgery (23 procedures). At the first radiosurgical procedure, the total volume of the AVM is estimated and a dose plan calculated that covers 10 cm(3)-15 cm(3), or one-half the nidus volume if the AVM is critically located (brainstem, thalamus, or basal ganglia). At 6-month intervals thereafter, radiosurgery was repeated to different portions of the AVM with the previous dose plan(s) being re-created utilizing intracranial landmarks to minimize radiation overlap. Radiosurgical procedures were continued until the entire malformation has been irradiated. RESULTS: The radiation dosimetry of staged-volume AVM radiosurgery was compared to hypothetical single-session procedures for the 10 patients. Staged-volume radiosurgery decreased the 12-Gy volume by an average of 11.1% (range, 4.9-21%) (p < 0.001). The non-AVM 12-Gy volume was reduced by an average of 27.2% (range, 12.5-51.3%) (p < 0.001). DISCUSSION: Staged-volume radiosurgery of large AVMs results in less radiation exposure to the adjacent brain. Further follow-up is needed to determine whether this technique provides a high rate of AVM obliteration while maintaining an acceptable rate of radiation-related complications.

Stereotactic radiosurgery for tumor-related trigeminal pain.

OBJECTIVE: Between 1 and 6% of patients who are diagnosed with facial pain syndromes have tumors that involve the trigeminal nerve. We report the effects of stereotactic radiosurgery on tumor-related trigeminal pain. METHODS: We reviewed results, from a prospective database, for 24 consecutive patients with cranial base tumors and either trigeminal neuralgia (n = 9) or painful trigeminal neuropathy (n = 15) who underwent stereotactic radiosurgery during an 8-year period. The tumor was the radiosurgical target for these patients (not the trigeminal nerve or ganglion). The median clinical follow-up period after radiosurgery was 45 months (range, 12-90 mo); the median neuroimaging follow-up period was 36 months (range, 5-86 mo). RESULTS: There were 20 women and 3 men, with an average age of 57 years (range, 33-79 yr). One patient had bilateral facial pain and underwent staged radiosurgery. Pathological classification indicated 16 meningiomas and 8 malignant cranial base tumors (adenoid cystic carcinoma, n = 6; squamous cell carcinoma, n = 2). Twelve of 24 patients (50%) were initially free of pain, and another 11 patients (46%) reported that they experienced significant improvements in their trigeminal pain syndromes after radiosurgery. The tumor histological type, quality of facial pain, preexisting facial numbness, and marginal and maximal radiation doses were not related to postradiosurgical facial pain outcomes. Three patients with malignant cranial base carcinomas developed recurrent facial pain, 1 to 9 months after radiosurgery, which was related to tumor progression outside the irradiated volume. One patient (4%) developed new partial V2 numbness after radiosurgery. CONCLUSION: Radiosurgery proved to be effective in improving tumor-related trigeminal pain for the majority of patients with either benign or malignant cranial base tumors. Recurrence of trigeminal pain is frequent for patients with malignant cranial base carcinomas and is related to tumor progression.

Stereotactic radiosurgery for recurrent ependymoma.

BACKGROUND: Patients with recurrent intracranial ependymomas were evaluated to assess local control, overall survival, and complications from stereotactic radiosurgery (SRS). METHODS: Twelve patients (with a total of 17 tumors) with recurrent ependymoma underwent SRS. Local failure was defined as tumor progression within the prescription isodose volume, and marginal failure was defined as tumor progression adjacent to the SRS prescription isodose volume. Tumor progression away from the prescription volume was considered distant failure. Eleven of the 12 patients had undergone previous resection and external beam radiation therapy (46-56 Grays [Gy]; median, 54 Gy) before radiosurgery, and 1 patient had failure after complete resection alone. Age at SRS ranged from 5-56 years (median, 29 years). Three patients were female. The marginal tumor dose was 12-24 Gy (median, 18 Gy). One to 14 isocenters (median, 4 isocenters) were utilized to irradiate volumes of 0.3-15.5 cm(3) (median, 3.2 cm(3)). RESULTS: The duration of follow-up ranged from 2.5-60 months (median, 22.5 months). The median overall survival after SRS was 3.4 years (range, 1.4-5 years). In-field local control was achieved in 14 of the 17 tumor sites and estimated 3-year local control was 68%. There were two in-field failures and one marginal failure. Distant failure occurred in two patients. Two patients developed treatment-related complications after SRS. CONCLUSIONS: SRS provides good local tumor control for patients with recurrent intracranial ependymoma and may have a favorable impact on survival. SRS should be evaluated more extensively in the initial treatment of patients with ependymoma to minimize local failure after surgical management.

Results of repeated gamma knife radiosurgery for medically unresponsive trigeminal neuralgia.

OBJECT: Gamma knife radiosurgery (GKS) is being increasing performed in the management of patients with medically unresponsive trigeminal neuralgia. The authors report the results of repeated GKS in patients with recurrent facial pain after their initial procedure. METHODS: Between April 1997 and December 1999, 100 patients with idiopathic trigeminal neuralgia underwent GKS at the authors' center. To date, 26 patients have required additional surgery because GKS provided no significant pain relief (15 patients) or because they had recurrent facial pain (11 patients). Ten of these patients underwent repeated GKS at a median of 13 months (range 4-27 months). All patients undergoing repeated GKS had a significant reduction in their facial pain after the first procedure (eight were pain free); no patient developed facial numbness or paresthesias. Initially, nine of 10 patients became pain free 1 to 4 weeks following repeated GKS. At a median follow up of 15 months (range 3-32 months), eight patients remained pain free and required no medication. All eight patients with persistent pain relief developed minor neurological dysfunction after repeated GKS (six patients had facial numbness and two had paresthesias). CONCLUSIONS: Repeated GKS can be associated with a high rate of pain relief for patients with trigeminal neuralgia who experienced a significant reduction in their facial pain after the first operation. However, every patient with sustained pain relief after the second operation also developed some degree of trigeminal dysfunction. These findings of improved pain relief for patients who develop facial numbness after GKS for trigeminal neuralgia support the experimental data currently available.

Frequency of noncontiguous lymph node involvement in patients with resectable nonsmall cell lung carcinoma.

BACKGROUND: This study was undertaken to investigate the patterns of lymph node spread and the frequency of involvement of noncontiguous lymph node stations in patients with nonsmall cell lung carcinoma who had complete surgical resection. METHODS: All patients who had surgical resection as their sole treatment for nonsmall cell lung carcinoma during the years 1987-1990 were reviewed. All patients were treated similarly. Generally, complete mediastinal lymph node dissection was performed after resection of the primary lesion and N1 lymph nodes. Patients were assessed for patterns of involvement of N1 and N2 lymph node stations. The frequency of noncontiguous involvement of lymph nodes (involvement of N2 lymph nodes without involvement of N1 lymph nodes) was determined. Patient and tumor characteristics were assessed to ascertain whether certain factors were likely to predict this noncontiguous pattern of lymph node spread. RESULTS: During the 4-year period of study, 336 patients with nonsmall cell lung carcinoma were managed with surgical resection alone. Of the 336, 100 had no involvement of lymph nodes, 108 had involvement of N1 lymph nodes only, 76 had involvement of N1 and N2 lymph nodes, and 52 had involvement of N2 lymph nodes only. Therefore, 52 of all 336 patients (15%) and 52 of 236 patients with lymph node involvement (22%) had noncontiguous lymph node spread. A review of the initial patient and tumor characteristics revealed that patients with a suggestion of enlarged mediastinal lymph nodes on preoperative computed tomography scans of the chest (compared with negative findings) and patients with T1 and T2 lesions (compared with T3 and T4) were more likely to have noncontiguous lymph node spread; the odds ratios (with 95% confidence intervals) were 2.18 (1.01-4.71) and 2.82 (1.36-5.84), respectively. CONCLUSIONS: Noncontiguous involvement of thoracic lymph nodes occurred in approximately 15% of patients who had complete surgical resection of nonsmall cell lung carcinoma. This factor suggests that lack of involvement of N1 lymph nodes does not rule out mediastinal involvement and provides important information for complete surgical staging.

Factors predicting patterns of recurrence after resection of N1 non-small cell lung carcinoma.

BACKGROUND: Although irradiation and chemotherapy are unproved adjuvant treatments for completely resected N1 non-small cell lung carcinoma, previous studies may have been diluted by the inclusion of low-risk patients. Risk factors in this situation, however, are not yet well defined. METHODS: One hundred seven consecutive patients with complete resection of N1 disease who received no other therapy were studied to identify factors independently predicting the risk of freedom from local recurrence (FFLR), freedom from distant metastasis (FFDM), and overall survival (OS). RESULTS: Twelve factors were assessed for a potential prognostic relationship with FFLR, FFDM, and OS. Regression analyses revealed that the factors independently associated with an improved outcome were positive bronchoscopic findings (FFLR, p = 0.005), a greater number of dissected N1 nodes (FFDM, p = 0.02), and a lesser T stage (OS, p = 0.01). Classification and regression tree analyses were then used to separate the patients into risk groups. CONCLUSIONS: Although these results require corroboration in further studies, they may aid the design of trials examining therapies used to decrease rates of local recurrence or distant metastasis.

Risk of injury to cranial nerves after gamma knife radiosurgery for skull base meningiomas: experience in 88 patients.

OBJECT: In this study the authors sought to determine the neurological risks and potential clinical benefits of gamma knife radiosurgery for skull base meningiomas. METHODS: A consecutive series of 88 patients harboring skull base meningiomas were treated between 1990 and 1996 by using the Leksell gamma knife in a prospective clinical study that included a strict dose-volume protocol. Forty-nine patients had previously undergone surgery, and six had received external-beam radiotherapy. The median treatment volume was 10 cm3, and the median dose to the tumor margin was 16 Gy. The radiosurgical dosage to the optic nerve, the cavernous sinus, and Meckel's cave was calculated and correlated with clinical outcome. The median patient follow-up time was 35 months (range 12-83 months). Two tumors (2.3%) progressed after radiosurgery; the progression-free 5-year survival rate was 95%. At last follow-up review, 60 (68%) tumors were smaller and 26 (29.5%) remained unchanged. Clinical improvement (in vision, trigeminal pain, or other cranial nerve symptoms) occurred in 15 patients. Functioning optic nerves received a median dose of 10 Gy (range 1-16 Gy), and no treatment-induced visual loss occurred. Among nine patients with new trigeminal neuropathy, six received doses of more than 19 Gy to Meckel's cave. CONCLUSIONS: Gamma knife radiosurgery appeared to be an effective method to control the growth of most skull base meningiomas in this intermediate-term study. The risk of trigeminal neuropathy seemed to be associated with doses of more than 19 Gy, and the optic apparatus appeared to tolerate doses greater than 10 Gy. Considering the risks to cranial nerves associated with open surgery for comparable tumors, the authors believe that gamma knife radiosurgery is a useful method for the management of properly selected recurrent, residual, or newly diagnosed skull base meningiomas.

Cerebral toxicity in patients treated for small cell carcinoma of the lung.

OBJECTIVE: To present the clinical characteristics of patients enrolled in a trial of treatment of small cell carcinoma (SCC) of the lung and to describe the central nervous system toxicity associated with the chemotherapy and prophylactic cranial irradiation (PCI). MATERIAL AND METHODS: We performed a retrospective analysis of 60 patients with SCC who received chemotherapy and thoracic radiation therapy. PCI was administered to patients who had limited disease or who had extensive disease that was subsequently down-staged to only residual chest disease after initial treatment. The total PCI dose was 3,200 cGy administered in 16 fractions of 200 cGy, given concurrently with systemic chemotherapy. Diagnostic criteria for leukoencephalopathy were based on previously published guidelines. RESULTS: Of the 60 eligible and enrolled patients, 35 received PCI and 25 did not. Leukoencephalopathy developed in 5 of the 35 patients (14%) who received PCI. The median age of the patients in whom leukoencephalopathy developed was 64 years (range, 57 to 69), and the median follow-up time was 59 months. The most common signs and symptoms of leukoencephalopathy were intellectual changes, memory alterations, and motor abnormalities. The mean time to onset of symptoms after termination of irradiation was 357 days (range, 30 to 524). Of all 60 patients, 6 were still alive 4 years after enrollment, and 3 of them (50%) already had leukoencephalopathy. CONCLUSION: Small dosage fractions of PCI may still result in leukoencephalopathy. The routine use of PCI in the management of SCC should be reassessed because of increasing evidence of the toxicity associated with it.