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 There was one post-operative death in a patient withdrawn from the trial, and no deaths related to hemorrhage.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 of a chlorhexidine mouthwash for alleviation of radiation-induced mucositis.

PURPOSE: To determine whether a chlorhexidine mouthwash could alleviate radiation-induced oral mucositis. PATIENTS AND METHODS: Patients scheduled to receive radiation therapy to include greater than one third of the oral cavity mucosa were selected for study. Following stratification, they were randomized in a double-blind manner to receive a chlorhexidine mouthwash or a placebo mouthwash. Both groups were then similarly evaluated for mucositis and mouthwash toxicity. RESULTS: Twenty-five patients were randomized to receive the chlorhexidine mouthwash, while 27 received the placebo mouthwash. Treatment arms were well balanced. There was a trend for more mucositis and there was substantially more toxicity (eg, mouthwash-induced discomfort, taste alteration, and teeth staining) on the chlorhexidine arm. CONCLUSION: In contrast to the prestudy hypothesis that a chlorhexidine mouthwash might provide benefit for patients receiving radiation therapy to the oral mucosa, this study provides strong evidence suggesting that a chlorhexidine mouthwash is detrimental in this clinical situation.

Limited-stage small-cell lung cancer: patterns of intrathoracic recurrence and the implications for thoracic radiotherapy.

PURPOSE: This analysis was performed to determine the most appropriate volume that should be encompassed by thoracic radiation treatments (TRTs) for patients with limited-stage small-cell lung cancer (LSSCLC) who have responded to initial chemotherapy. PATIENTS AND METHODS: A retrospective review of all patients (N = 67) with LSSCLC who were not entered onto a research protocol and were treated at our institution between the years of 1982 and 1990 was performed. Fifty-nine of 67 patients had adequate information regarding the size of the tumor before the start of chemotherapy (computed tomographic [CT] scan of chest or chest x-ray), the size of the tumor before TRT, and the TRT field size based on a simulation radiography. All 59 patients were treated with cyclophosphamide-based chemotherapy, and TRT was generally delivered concomitantly with chemotherapy following two to three cycles of chemotherapy alone. RESULTS: Of 59 patients, 28 were treated with TRT field sizes that encompassed postchemotherapy tumor volumes, and 31 patients were treated with TRT field sizes that encompassed prechemotherapy tumor volumes (defined as a volume that included at least a 1.5-cm margin on the prechemotherapy tumor volume). Nineteen patients had an intrathoracic recurrence of disease as the first site of recurrent small-cell carcinoma: 10 of 31 patients treated with TRT fields that encompassed prechemotherapy tumor volumes and nine of 28 patients treated with TRT fields that encompassed postchemotherapy tumor volumes. For the 28 patients treated with TRT fields that encompassed postchemotherapy tumor volumes, the greatest distance that the prechemotherapy tumor volume (without margins) extended beyond the edge of the TRT field was 0.5 to 5.0 cm, with a median of 2.5 cm. All 19 of the intrathoracic recurrences were in-field failures, although two patients (one prechemotherapy volume and one postchemotherapy volume) did have concurrent pleural effusions. CONCLUSION: These results indicate that the use of TRT fields that encompass postchemotherapy tumor volumes does not increase the risk of marginal failures or intrathoracic failures outside the TRT field.

Alleviation of cytotoxic therapy-induced normal tissue damage.

Cytotoxic chemotherapy and radiation therapy damage normal body tissues, resulting in stomatitis, conjunctivitis, esophagitis, proctitis, and dermatitis. Pursuant to this, the North Central Cancer Treatment Group has developed a series of clinical trials designed to study antidotes for these pathologic processes. These trials have demonstrated clinically helpful therapies (eg, oral cryotherapy for decreasing mucositis induced by 5-fluorouracil) and also have demonstrated lack of benefit for other proposed treatments. Results from several ongoing clinical trials should become available in the near future.

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.

Radiation treatment of heterotopic bone formation in the temporomandibular joint articulation.

PURPOSE: The efficacy and toxicity of radiation therapy used for preventing re-formation of heterotopic bone involving the temporomandibular joint are assessed. METHODS AND MATERIALS: Ten patients (15 TMJs) with bony ankylosis of the TMJ were referred after reconstruction with costochondral graft, gap arthroplasty, or debridement of heterotopic bone. Treatment consisting of 10 Gy was delivered early postoperatively to a field encompassing the TMJ with adequate margin. Response to therapy was assessed by comparison of routine roentgenograms obtained preoperatively, immediately postoperatively, and at last follow-up; the Turlington-Durr grading system was used. Median duration of postoperative follow-up was 19 months. RESULTS: Radiation therapy prevented ectopic bone re-formation in 10 (69%) of 15 TMJs with prior bony ankylosis. Of the 15 TMJs, 13 (87%) had improvement in their Turlington-Durr scores compared with the preoperative scores. Development of ectopic bone formation was prevented in 9 (90%) of 10 TMJs rendered Turlington-Durr grade 0 postoperatively. Eight of the 10 patients have remained asymptomatic. Treatment was well tolerated. The only complication experienced was parotitis in three patients. CONCLUSION: Radiation therapy is useful for prevention of heterotopic bone redevelopment after TMJ operation. We recommend 10 Gy in 5 fractions beginning early postoperatively for high-risk patients. This strategy appears beneficial in this young patient population, who suffer significant pain and functional impairment in the TMJ articulation.

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.

Doses to radiation sensitive organs and structures located outside the radiotherapeutic target volume for four treatment situations.

This study documents dosage to radiation sensitive organs/structures located outside the radiotherapeutic target volume for four treatment situations: (a) head and neck, (b) brain (pituitary and temporal lobe), (c) breast and (d) pelvis. Clinically relevant treatment fields were simulated on a tissue-equivalent anthropomorphic phantom and subsequently irradiated with Cobalt-60 gamma rays, 6- and 18-MV x-ray beams. Thermoluminescent dosimeters and diodes were used to measure absorbed dose. The head and neck treatment resulted in significant doses of radiation to the lens and thyroid gland. The total treatment lens dose (300-400 cGy) could be cataractogenic while measured thyroid doses (1000-8000 cGy) have the potential of causing chemical hypothyroidism, thyroid neoplasms, Graves' disease and hyperparathyroidism. Total treatment retinal (400-700cGy) and pituitary (460-1000 cGy) doses are below that considered capable of producing chronic disease. The pituitary treatment studied consisted of various size parallel opposed lateral and vertex fields (4 x 4 through 8 x 8 cm). The lens dose (40-200 cGy) with all field sizes is below those of clinical concern. Parotid doses (130-1200 cGy) and thyroid doses (350-600 cGy) are in a range where temporary xerostomia (parotid) and thyroid neoplasia development are a reasonable possibility. The retinal dose (4000 cGy) from the largest field size (8 x 8 cm2) is in the range where retinopathy has been reported. The left temporal lobe treatment also used parallel opposed lateral and vertex fields (7 x 7 and 10 x 10 cm). Doses to the pituitary gland (5200-6200 cGy), both parotids (200-6900 cGy), left lens (200-300 cGy) and left retina (1700-4500 cGy) are capable of causing significant future clinical problems. Right-sided structures received insignificant doses. Secondary malignancies could result from measured total treatment thyroid doses (670-980 cGy). Analysis of three breast/chest wall and regional nodal irradiation techniques demonstrated a 25-50% decrease in secondary lung dose with use of independent collimation compared to use of custom alloy blocking material. However, it is unlikely that a reduction in secondary dose of this magnitude would reduce the risk of treatment sequellae. In four-field "box" pelvic irradiation, secondary testes dose may result in temporary (clamshell shield) or permanent azoospermia, but is unlikely to impair androgen production.

Adjuvant radiotherapy for squamous cell carcinoma of the tongue base: improved local-regional disease control compared with surgery alone.

PURPOSE: The purpose of this retrospective study is to present the results of postoperative adjuvant radiotherapy after primary surgery for squamous cell carcinoma of the tongue base and to compare these results to those obtained with surgery alone. METHODS: Between 1974 and 1993, continuous-course postoperative radiotherapy was delivered to 24 patients (Adjuvant Radiotherapy Group). Results were compared to those from a group of 55 patients treated with surgery alone (Surgery Group). RESULTS: Characteristics of the two groups were similar, except that a larger proportion of patients in the Adjuvant Radiotherapy Group had higher pathologic TNM stages. Ipsilateral neck control (87% vs. 68%, p = 0.04), contralateral neck control (100% vs. 76%,p = 0.002), relapse-free survival (64% vs. 46%,p = 0.04), and control above the clavicles (80% vs. 48%, p = 0.007) were significantly higher in the Adjuvant Radiotherapy Group compared to those in the Surgery Group (5-year figures shown). CONCLUSION: The use of adjuvant radiotherapy after surgical resection of tongue base squamous cell carcinoma significantly decreased the rate of local-regional recurrence and improved relapse-free survival compared with surgery alone but did not alter cause-specific or overall survival.

External beam irradiation for retinoblastoma: patterns of failure and dose-response analysis.

Eighteen children with retinoblastoma (25 eyes) were treated with external beam radiation at the Mayo Clinic between January 1977 and January 1987; 15 eyes were in groups I to III and 10 were in groups IV and V (Reese-Ellsworth classification). The median number of tumors per eye was 3. Radiation therapy consisted of 4- or 6-MV photons. Doses varied from 39 to 51 Gy in 1.8- to 3.0-Gy fractions. Fourteen eyes were treated through lateral fields by anterior segment-sparing techniques, and 11 eyes were treated by an anterior approach with no attempt at anterior segment sparing. All patients survived (median follow-up, 31.5 months). Cataracts developed in five eyes at a median of 23 months, four in eyes treated with anterior segment-sparing techniques. Of the 15 group I to III eyes, 6 required additional treatment; 4 were salvaged with cryotherapy or photocoagulation and 2 were enucleated. Of the 10 group IV and V eyes, 8 required additional treatment; 4 were salvaged with cryotherapy or photocoagulation, 1 with persistent disease is being followed closely, and 3 were enucleated. Ten (71%) of the 14 eyes treated with anterior segment-sparing techniques required additional treatment (9 of the 10 for tumors anterior to the equator). Four (36%) of the 11 eyes treated with an anterior approach required additional treatment (3 of the 4 for tumors in the posterior pole of group IV or V eyes). Ninety percent of the tumors 10 disc diameters or smaller (1 disc diameter = 1.6 mm) were controlled independently of dose and fractionation used when they were not in the low-dose area of the anterior retina of an eye treated with an anterior segment-sparing technique. We find that use of lateral, anterior segment-sparing techniques has a high risk of anterior retinal tumor development and cataract formation and should be abandoned in favor of techniques that treat the entire retina. A dose of 45 Gy in 1.8-Gy fractions appears to be adequate for local control of tumors smaller than 10 disc diameters. Larger tumors may require additional treatment.

Esthesioneuroblastoma: the role of adjuvant radiation therapy.

PURPOSE: We describe our experience with adjuvant radiation therapy in patients who underwent operation for esthesioneuroblastoma. METHODS AND MATERIALS: Between January 1951 and December 1990, 49 patients with esthesioneuroblastoma received their initial treatment at the Mayo Clinic. There were 27 male and 22 female patients; their ages ranged from 3 to 79 years (median, 54 years). The tumors were Kadish Stage A in 4 patients, Stage B in 13, Stage C in 29, and modified Kadish Stage D in three (cervical nodal or distant metastasis). The tumors were graded according to Hyams' classification. Treatment included gross total resection alone in 22 patients and gross total resection and postoperative adjuvant radiation therapy in 16. The patients treated with adjuvant radiation had a greater proportion of advanced-stage and high-grade tumors. RESULTS: The 5-year actuarial overall survival, disease-free survival, and local control rates were 69.1% + 7.0%, 54.8% + 7.6%, and 65.3% + 7.4%, respectively. The only significant predictor for overall survival, disease-free survival, and local control was Hyams' grade. Local control was improved in patients who received postoperative adjuvant radiation even though this group of patients had more advanced and higher-grade tumors (5-year rate of local control was 85.9% + 9.3%, compared with 72.7% + 9.5% for those who had operation alone, p = 0.26). CONCLUSION: Adjuvant radiation therapy for esthesioneuroblastoma improves local tumor control, particularly for high-grade and high-stage tumors. We recommend additional treatment with radiation (55.5 Gy) after complete resection of esthesioneuroblastoma.

Stereotactic radiosurgery using the gamma knife for acoustic neuromas.

PURPOSE: To assess the efficacy and toxicity of stereotactic radiosurgery using the gamma knife for acoustic neuromas. METHODS AND MATERIALS: Between January 1990 and January 1993, 36 patients with acoustic neuromas were treated with stereotactic radiosurgery using the gamma knife. The median maximum tumor diameter was 21 mm (range: 6-32 mm). Tumor volumes encompassed within the prescribed isodose line varied from 266 to 8,667 mm3 (median: 3,135 mm3). Tumors < or = 20 mm in maximum diameter received a dose of 20 Gy to the margin, tumors between 21 and 30 mm received 18 Gy, and tumors > 30 mm received 16 Gy. The dose was prescribed to the 50% isodose line in 31 patients and to the 45%, 55%, 60%, 70%, and 80% isodose line in one patient each. The median number of isocenters per tumor was 5 (range: 1-12). RESULTS: At a median follow-up of 16 months (range: 2.5-36 months), all patients were alive. Thirty-five patients had follow-up imaging studies. Nine tumors (26%) were smaller, and 26 tumors (74%) were unchanged. No tumor had progressed. The 1- and 2-year actuarial incidences of facial neuropathy were 52.2% and 66.5%, respectively. The 1- and 2-year actuarial incidences of trigeminal neuropathy were 33.7% and 58.9%, respectively. The 1- and 2-year actuarial incidence of facial or trigeminal neuropathy (or both) was 60.8% and 81.7%, respectively. Multivariate analysis revealed that the following were associated with the time of onset or worsening of facial weakness or trigeminal neuropathy: (a) patients < age 65 years, (b) dose to the tumor margin, (c) maximum tumor diameter > or = 21 mm, (d) use of the 18 mm collimator, and (e) use of > five isocenters. The 1- and 2-year actuarial rates of preservation of useful hearing (Gardner-Robertson class I or II) were 100% and 41.7% +/- 17.3, respectively. CONCLUSION: Stereotactic radiosurgery using the gamma knife provides short-term control of acoustic neuromas when a dose of 16 to 20 Gy to the tumor margin is used. Preservation of useful hearing can be accomplished in a significant proportion of patients.

Cervical nodal metastasis of squamous cell carcinoma of unknown origin: indications for withholding radiation therapy.

The records of patients with pathologically confirmed metastatic squamous cell carcinoma involving cervical lymph nodes who were treated at the Mayo Clinic between January 1965 and December 1987 were reviewed. In 117 patients a primary tumor could not be discovered. Of these, 24 patients underwent curative resection of all gross disease by neck dissection or excisional biopsy. All 24 patients presented with unilateral adenopathy. Their median age was 63 years. Eighteen patients were men. Fourteen patients were in clinical stage N1; six, N2a; three, N2b; and one, N3. Six patients had grade 1 or 2 nodal metastases; 14, grade 3; and 4, grade 4. Gross or microscopic evidence of extracapsular tumor extension was noted in eight patients. All patients were followed until death or for a median of 8.5 years (range, 3.3-20.4 years). A squamous cell carcinoma of the upper aerodigestive tract subsequently developed in only one patient (4%) within 5 years of operation. In six patients (25%), a recurrence developed in the dissected neck a median of 3 months (2.4 months-6.6 years) after operation. Five of these patients had extracapsular extension, and four had pathologic Stage N2a or higher neck disease. Both patients with pathologic Stage N1 disease who had recurrences in the dissected neck had extracapsular extension. Delayed, contralateral neck metastases in an undissected neck developed in two patients. The 5-year overall and cause-specific survivals for all 24 patients were 66% and 74%, respectively. Extracapsular extension was a predictor of neck recurrence, control of disease above the clavicles, cause-specific survival, and overall survival. Patients with pathologic Stage N1 neck disease with no extracapsular extension can be managed by surgery alone. Patients with pathologic Stage N2 or higher neck disease or extracapsular extension should be considered for postoperative, adjuvant radiation therapy.

Stereotactic radiosurgery for glomus jugulare tumors: a preliminary report.

PURPOSE: This study was conducted to evaluate the toxicity and efficacy of stereotactic radiosurgery treatment of glomus jugulare tumors. METHODS AND MATERIALS: Between March 1990 and January 1995, nine patients underwent stereotactic radiosurgery with the Leksell Gamma Knife Unit for glomus jugulare tumors. Previous treatment had failed in four patients. The seven female and two male patients had a median age of 67 years. RESULTS: The median time from stereotactic radiosurgery to the most recent clinical follow-up was 20 months (range 7-65 months). Subjectively, 7 of 9 patients noted a decrease in the intensity of their symptoms. Objectively, 8 of 9 tumors remained stable in size by serial magnetic resonance imaging scans and one was smaller. There was no acute or chronic toxicity. CONCLUSION: This early experience suggests that stereotactic radiosurgery is a promising treatment for glomus jugulare tumors.

The role of stereotactic radiosurgery in the treatment of malignant skull base tumors.

PURPOSE: To determine the efficacy and toxicity of stereotactic radiosurgery in the treatment of malignant skull base tumors. METHODS AND MATERIALS: Thirty-two patients with 35 newly diagnosed or recurrent malignant skull base tumors < or = 33.5 cm3 were treated using the Leksell Gamma unit. Tumor histologies included: adenoid cystic carcinoma [12], basal cell carcinoma [1], chondrosarcoma [1], chordoma [8], nasopharyngeal carcinoma [3], osteogenic sarcoma [2], and squamous cell carcinoma [8]. RESULTS: After a median follow-up of 2.3 years, 83% +/- 15% (+/-95% confidence interval) of patients experienced a symptomatic response to treatment. Local control at the skull base was 95 +/- 9% at 2 years and 78 +/- 23% at 3 years. Local-regional control above the clavicles was 75 +/- 15% at 1 year and 51 +/- 20% at 2 years. Overall and cause specific survival were identical, 82 +/- 13% at 1 year, 76 +/- 14% at 2 years, and 72 +/- 16% at 3 years. One patient developed a radiation-induced optic neuropathy 12 months after radiosurgery. CONCLUSION: Stereotactic radiosurgery using the Leksell Gamma Unit can provide durable tumor control and symptomatic relief with acceptable toxicity in the majority of patients with malignant tumors 4 cm or less in size involving the skull base. Further evaluation of more patients with longer follow-up is warranted.

Spinal cord localization in the treatment of lung cancer: use of radiographic landmarks.

PURPOSE: In the treatment of thoracic malignancies with radiotherapy, the critical dose-limiting structure is the spinal cord. Oblique fields typically are designed to exclude the spinal cord, and by convention, the field edge that shields the spinal cord is placed at the anterior border of the vertebral pedicles. Thus, the purpose of our study was to estimate the distance between the field edge and spinal cord in oblique fields that were designed by using the vertebral pedicle as a radiographic landmark. METHODS AND MATERIALS: The spinal cord of a cadaver was wrapped in wire, and oblique fields were simulated at 15 degree intervals. The distance from the spinal cord to a field edge placed at the anterior border of the pedicle was measured. In the second investigation, a three-dimensional treatment planning system was used to simulate hypothetical fields using actual patient data from computed tomography (n = 10), and measurements identical to those in the anatomical model were made (n = 1,100). RESULTS: The results of the anatomical and computed tomographic models were in close agreement (mean difference, 0.6 mm). The computed tomographic model predicted a mean field edge to spinal cord distance of 8.7 mm (95% confidence interval, 5.6-11.8 mm) for 30 degree/150 degree oblique fields and 8.0 mm (95% confidence interval, 4.7-11.7 mm) for 45 degree/135 degree oblique fields. This distance was greatest at levels T-1, T-2, and T-11 (8 to 20% greater). CONCLUSIONS: The mean distance from a field edge placed at the anterior border of a vertebral pedicle to the spinal cord for commonly used oblique angles constitutes a sufficient margin to account for expected differences in daily positional variations and mechanical uncertainties.

Decrease in cranial nerve complications after radiosurgery for acoustic neuromas: a prospective study of dose and volume.

PURPOSE: To determine whether tumor control can be maintained, and cranial nerve complications decreased by reducing the radiosurgical dose to acoustic neuromas. METHODS AND MATERIALS: Forty-two consecutive patients with acoustic neuromas were treated prospectively using an initial standard-dose protocol in which the tumor-margin dose (50% isodose) was 20, 18, and 16 Gy for tumor diameters < or =2 cm, 2.1-3 cm, and 3.1-4 cm, respectively. After analysis of tumor control and complications, the next 40 patients were treated using a reduced-dose protocol in which the tumor-margin dose was 16, 14, and 12 Gy for tumor volumes < or =4.2 cm3, 4.2-14.1 cm3, and > or =14.1 cm3, respectively. RESULTS: Median follow-up was 2.3 years (range 0.1-6) for 80 of 82 patients. The actuarial incidence (Kaplan-Meier) of facial neuropathy at 2 years was 38% (95% confidence interval [CI], 23-53%) for the standard-dose protocol and 8% (95% CI, 0-17%) for the reduced-dose protocol (p = 0.006). Univariate analysis revealed an association between risk of facial neuropathy and use of CT planning, higher radiosurgical dose, and neurofibromatosis, type 2. Multivariate analysis revealed that the only factor associated with increased risk of post-treatment facial neuropathy was a tumor margin dose > or =18 Gy. The incidence of trigeminal neuropathy at 2 years was 29% (95% CI, 15-43%) for the standard-dose protocol and 15% (95% CI, 3-27%) for the reduced-dose protocol (p = 0.17). Univariate analysis revealed an association between maximal tumor diameter and increased risk of trigeminal neuropathy; multivariate analysis revealed no additional statistically significant associations between tumor and dosimetric and patient characteristics and risk of trigeminal neuropathy. Two tumors in the standard-dose protocol required salvage surgery for progression. To date, no tumor in the reduced-dose protocol has shown progression. CONCLUSION: Our analysis suggests that a tumor margin dose of > or =18 Gy is the most significant risk factor for facial nerve complications after acoustic neuroma radiosurgery. Patients receiving a minimal tumor dose of < or =16 Gy are at significantly lower risk for permanent facial neuropathy after radiosurgery. Longer follow-up is required before definitive conclusions can be made about the ultimate rate of tumor control using reduced radiosurgical doses.

Predictors of subclinical nodal involvement in clinical stages I and II non-small cell lung cancer: implications in the inoperable and three-dimensional dose-escalation settings.

PURPOSE: When mediastinal lymph nodes are clinically uninvolved in the setting of inoperable non-small cell lung cancer, whether conventional radiation techniques or three-dimensional dose-escalation techniques are used, the benefit of elective nodal irradiation is unclear. Inclusion of the clinically negative mediastinum in the radiation portals increases the risk of lung toxicity and limits the ability to escalate dose. This analysis represents an attempt to use clinical characteristics to estimate the risk of subclinical nodal involvement, which may help determine which patients are most likely to benefit from elective nodal irradiation. METHODS: From 1987 to 1990, 346 patients undergoing complete resection of non-small cell lung cancer underwent a preoperative computed tomographic scan revealing no clinical evidence of N2/N3 involvement. Multivariate regression and regression tree analyses attempted to define which patients were at highest risk for subclinical mediastinal involvement (N2) and which patients were at highest risk for subclinical N1 and/or N2 involvement (N1/N2). Immunohistochemical data suggest that the conventional histopathologic techniques used during this study somewhat underestimate the true degree of lymph node involvement; therefore, a third end point was also evaluated: N1 involvement and/or N2 involvement and/or local-regional recurrence (N1/N2/LRR). RESULTS: Regression analyses revealed that the following factors were independently associated with a high risk of more advanced disease: positive preoperative bronchoscopy (N2, p = 0.02; N1/N2, p < 0.0001; N1/N2/LRR, p < 0.001) and tumor grade 3/4 (N1/N2/LRR, p < 0.01). A regression tree analysis was then used to separate patients into risk groups with respect to N1/N2/LRR. CONCLUSION: In inoperable non-small cell lung cancer, the patients for whom mediastinal radiation therapy may most likely be indicated are those with a positive preoperative bronchoscopy, especially with large (> 3 cm) primary tumors.