Quantifying the severity of sarcopenia in patients with cancer of the head and neck.

BACKGROUND & AIMS: Existing skeletal muscle index (SMI) thresholds for sarcopenia are inconsistent, and do not reflect severity of depletion. In this study we aimed to define criterion values for moderate and severe skeletal muscle depletion based on the risk of mortality in a population of patients with head and neck cancer (HNC). Additionally, we aimed to identify clinical and demographic predictors of skeletal muscle depletion, evaluate the survival impact of skeletal muscle depletion in patients with minimal nutritional risk or good performance status, and finally, benchmarking SMI values of patients with HNC against healthy young adults. METHODS: Population cohort of 1231 consecutive patients and external validation cohorts with HNC had lumbar SMI measured by cross-sectional imaging. Optimal stratification determined sex-specific thresholds for 2-levels of SMI depletion (Class I and II) based on overall survival (OS). Adjusted multivariable regression analyses (tumor site, stage, performance status, age, sex, dietary intake, weight loss) determined relationships between 2-levels of SMI depletion and OS. RESULTS: Mean SMI (cm2/m2) was 51.7 ± 9.9 (males) and 39.8 ± 7.1 (females). The overall and sex-specific population demonstrated an increased risk of mortality associated with decreasing SMI. Sex-specific SMI (cm2/m2) depletion thresholds for 2-levels of muscle depletion determined by optimal stratification for males and females, respectively (male: 45.2-37.5, and <37.5; female: 40.9-34.2, and <34.2). In the overall population, Normal SMI, Class I and II SMI depletion occurred in 65.0%, 24.0%, and 11.0%, respectively. Median OS was: Normal SMI (114 months, 95% CI, 97.1-130.8); Class I SMI Depletion (42 months, 95% CI, 28.5-55.4), and Class II SMI Depletion (15 months, 95% CI, 9.8-20.1). Adjusted multivariable analysis compared with Normal SMI (reference), Class I SMI Depletion (HR, 1.49; 95% CI, 1.18-1.88; P < .001), Class II SMI Depletion (HR, 1.91; 95% CI, 1.42-2.58; P < .001). CONCLUSIONS: Moderate and severe SMI depletion demonstrate discrimination in OS in patients with HNC. Moderate and severe SMI depletion is prevalent in patients with minimal nutrition risk and good performance status. Benchmarking SMI values against healthy young adults exemplifies the magnitude of SMI depletion in patients with HNC and may be a useful method in standardizing SMI assessment.

Prevalence and prognostic significance of malnutrition in patients with cancers of the head and neck.

BACKGROUND & AIMS: Head and neck cancer (HNC) are at high nutritional risk; however the prevalence and severity of malnutrition in contemporary patients with HNC are unclear. Diagnostic criteria for cancer-associated weight loss grading (WLG) (Grades 0 to 4) [1] have been validated and are recommended in oncology nutrition clinical practice guidelines [2-3]. The aim was to determine the prevalence using WLG in HNC patients and determine the extent to which reduced dietary intake (DI) explained variation of WLG. METHODS: A population-based cohort of HNC patients (N = 1756) in northern Alberta, Canada included consecutive new patients, 2004-2016. At referral to the regional cancer center weight history and DI categories were collected. Multinomial logistic regression (MLR) identified predictors of weight loss (WL) severity. Overall survival (OS) in relation to WL Grade and DI was determined by multivariable Cox proportional hazard. RESULTS: WL was absent in 42.9% and the remainder had Grade 1 (18%), Grade 2 (14.7%), Grade 3 (15.9%) and Grade 4 (8.5%) WL. Independent predictors of WLG in adjusted MLR model, included stage (P < 0.000), performance status (PS) (P < 0.000) and DI categories (P < 0.000); sex, age and disease site were not significant. Compared to "normal food in normal amount" adjusted Odds Ratio for WL Grade 4 was 4.0 (2.1-7.5) "normal food, but less than normal amount"; 25.2 (10.7-59.1) "little solid food"; 51.8 (10.5-255.3) "very little of anything"; 42.4 (11.0-163.0) "only liquids"; 25.9 (7.1-94.3) "only nutritional supplements". In the Cox model controlled for age, sex, cancer stage and site and PS, both WLG ((P < 0.000) and DI categories (P = 0.003) independently predicted OS. CONCLUSION: Data from this population cohort provide a benchmark for prevalence of cancer associated WL severity at diagnosis. Patient reported DI categories are strong predictors of WL and prognostic for OS.

Functional outcomes of the modified submandibular gland transfer procedure.

OBJECTIVES: Treatment for advanced head and neck cancers typically includes surgery followed by radiation therapy (RT). Radiation-induced xerostomia is a common sequela of these treatments. The modified submandibular gland transfer (M-SGT) procedure was developed to decrease xerostomia in the treatment of oral cavity cancer by sparing one submandibular gland (SMG) from radiation. This study's objectives were to: 1) elucidate the radiation-sparing capacity of the M-SGT, and 2) study the xerostomia-reducing potential of the M-SGT based on the University of Washington Quality-of-Life Questionnaire (UW-QOL). METHODS: Radiation therapy treatment plans were reviewed for all patients treated with surgery and RT who had a M-SGT at the University of Alberta Hospital during the study period. Outcomes included: 1) radiation dose received by the transferred SMG within the periparotid area compared to the submandibular triangle (ST), and 2) patient-reported saliva scores on the UW-QOL compared to historical controls without a gland transfer. RESULTS: Twenty-two patients were included. The mean radiation dose received by the transferred SMG was 29.00 grays (Gy) (standard deviation 14.59 Gy), thus reducing the mean radiation dose to the SMG by a statistically significant 18.34 Gy (confidence interval 95% (13.37, 23.32), P < 0.01) compared to the ST and below the D50 of the SMG (34 Gy). Sixty-five percent of patients rated their saliva as normal or mildly reduced on the UW-QOL as compared to 16% of controls (P = 0.01). CONCLUSION: The M-SGT technique is successful at reducing the radiation dose sustained by the SMG during adjuvant treatment and provides a significant improvement in xerostomia-related functional outcomes as compared to historical controls not receiving a gland transfer. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:925-929, 2020.

Should Stereotactic Radiosurgery Be Considered for Salvage of Intracranial Recurrence after Prophylactic Cranial Irradiation or Whole Brain Radiotherapy in Small Cell Lung Cancer? A Population-Based Analysis and Literature Review.

BACKGROUND: Prophylactic cranial irradiation (PCI) improves survival and prevents intracranial recurrence (IR) in limited stage (LS) and extensive stage (ES) small cell lung cancer (SCLC). However, despite PCI, IR affects 12%-45%, and limited data exist regarding salvage brain reirradiation (ReRT). We performed a population-based review of IR in SCLC. METHODS: Demographic, treatment, and outcome data of consecutive patients (N = 371) with SCLC assessed at a tertiary cancer centre (01/2013-12/2015) were abstracted, and summary statistics calculated. Kaplan-Meier estimates and univariate and multivariate analysis (MVA) via the Cox proportional hazard model were performed. RESULTS: Median age was 66.1 years, and 59.8% were Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Median survival was 24 months (95% CI 18.3-29.7 months) for LS (N = 103) and 7 months (95% CI 6.1-7.9 months) for ES (N = 268). 72 of 103 patients with LS and 97 of 214 of those with ES received PCI. 54 of 268 ES presented with brain metastases (BM) of whom 46 of 54 received whole brain RT (WBRT). 18.9% (32/169) recurred post-PCI (13 LS; 19 ES) and 30.4% (14/46) recurred after WBRT. Of those who recurred/progressed after cranial RT, 56.5% (26/46) had <5 BM, 39.1% had no extracranial disease, and 50% were ECOG 0-2. In retrospect, 17 of 46 would have been candidates for salvage stereotactic radiosurgery: 13 post-PCI and 4 post-WBRT. CONCLUSIONS: This cohort challenges commonly held beliefs that IR is always diffuse, associated with clinical deterioration, and synchronous with systemic failure. Approximately 1 in 3 SCLC patients with IR after PCI or WBRT appear clinically appropriate for salvage stereotactic radiosurgery.

Combination of submandibular salivary gland transfer and intensity-modulated radiotherapy to reduce dryness of mouth (xerostomia) in patients with head and neck cancer.

BACKGROUND: Xerostomia is a debilitating side effect of radiotherapy for head and neck cancer. Combining surgical submandibular-gland transfer (SMGT) with intensity-modulated radiotherapy (IMRT) may provide greater protection of salivary function. METHODS: This was a single-institution, prospective phase II feasibility trial. Patients with head and neck cancer or unknown primary with neck node metastases received primary surgery with SMGT and postoperative radiotherapy with tomotherapy (60 Gy in 30 fractions). Toxicity and quality of life (QOL) were assessed before surgery, before RT, and after RT. RESULTS: Forty patients received SMGT and IMRT. Only 1 patient experienced grade 3 salivary gland toxicity. At 12 months post-RT, the rate of absent or only mild xerostomia was 89%, and salivary flow rates were approximately 75% of pre-RT levels. CONCLUSIONS: The combination of IMRT with SMGT is feasible and with improved dose constraints may maximally spare the parotid and submandibular glands, leading to decreased xerostomia and improved patient QOL.

Free thyroid transfer: Short-term results of a novel procedure to prevent post-radiation hypothyroidism.

BACKGROUND: The incidence of radiation-induced hypothyroidism (RIH) in patients with head and neck cancer is >50%. The purpose of this study was to assess the long-term efficacy of free thyroid transfer (FTT) for prevention of RIH in patients with head and neck cancer. METHODS: Hemithyroid dissection was completed in 10 patients with advanced head and neck cancer undergoing ablation, radial forearm free flap (RFFF) reconstruction, and postoperative radiotherapy (RT). The hemithyroid was anastomosed to the donor site vessels in the forearm. Thyroid laboratory testing and technetium (Tc) scans were performed 6 weeks and 12 months postoperatively to establish functional integrity. RESULTS: FTT was successfully performed in 9 of 10 recruited patients. Postoperative Tc scans demonstrated strong Tc uptake in the forearm donor site at 6 weeks and 12 months in all patients who underwent transplantations. CONCLUSION: FTT is feasible with maintenance of function, and may represent a novel strategy for prevention of RIH. © 2016 Elsevier Head & Neck Published by Wiley Periodicals, Inc. Head Neck 39: 1234-1238, 2017.

Dose-escalated Hypofractionated Intensity-modulated Radiation Therapy With Concurrent Chemotherapy for Inoperable or Unresectable Non-Small Cell Lung Cancer.

PURPOSE: The local control of inoperable non-small cell lung cancer (NSCLC) using standard radiotherapy (RT) doses is inadequate. Dose escalation is a potential strategy to improve the local control for patients with NSCLC; however, the optimal dose required for local control in this setting is unknown. METHODS AND MATERIALS: Patients with unresectable or inoperable stage II/III NSCLC with ECOG≤1 received 48 Gy in 20 daily fractions using intensity-modulated radiotherapy, followed by 1 of 3 boost dose levels: 16.8 Gy/7 (cumulative 2 Gy equivalent dose [EQD2]≅76 Gy/38), 20.0 Gy/7 (EQD2≅84 Gy/42), and 22.7 Gy/7 (EQD2≅92 Gy/46). Two cycles of cisplatin/etoposide chemotherapy were given concurrent with RT. The maximum tolerated dose was defined as the dose at which ≥30% experienced dose-limiting toxicity (any NCIC Common Terminology for Adverse Events V3.0 grade 3 or higher acute toxicity). RESULTS: Twelve patients completed treatment with a median follow-up of 22 months (range, 7 to 48). The median age was 72 (range, 54 to 80) and 50% of patients had adenocarcinoma. Five, 3, and 4 patients were treated on dose levels 1, 2, and 3, respectively. No dose-limiting toxicity was observed. One-year local progression-free survival and overall survival estimates were 81% and 58%, respectively. CONCLUSIONS: Hypofractionated intensity-modulated radiotherapy was well tolerated and provided meaningful local control for patients with locally advanced inoperable NSCLC. The maximum tolerated dose of RT in this setting lies beyond an EQD2 of 92 Gy/46 and further dose escalation in this setting is warranted.

Survival Outcomes and Patterns of Recurrence in Patients with Stage III or IV Oropharyngeal Cancer Treated with Primary Surgery or Radiotherapy.

PURPOSE: To compare and contrast the patterns of failure in patients with locally advanced squamous cell oropharyngeal cancers undergoing curative-intent treatment with primary surgery or radiotherapy +/- chemotherapy. METHODS AND MATERIALS: Two hundred and thirty-three patients with stage III or IV oropharyngeal squamous cell carcinoma who underwent curative-intent treatment from 2006-2012, were reviewed. The median length of follow-up for patients still alive at the time of analysis was 4.4 years. Data was collected retrospectively from a chart review. RESULTS: One hundred and thirty-nine patients underwent primary surgery +/- adjuvant therapy, and 94 patients underwent primary radiotherapy +/- chemotherapy (CRT). Demographics were similar between the two groups, except primary radiotherapy patients had a higher age-adjusted Charleston co-morbidity score (CCI). Twenty-nine patients from the surgery group recurred; 15 failed distantly only, seven failed locoregionally, and seven failed both distantly and locoregionally. Twelve patients recurred who underwent chemoradiotherapy; ten distantly alone, and two locoregionally. One patient who underwent radiotherapy (RT) alone failed distantly. Two and five-year recurrence-free survival rates for patients undergoing primary RT were 86.6% and 84.9% respectively. Two and five-year recurrence-free survival rates for primary surgery was 80.9% and 76.3% respectively (p=0.21). There was no significant difference in either treatment when they were stratified by p16 status or smoking status. CONCLUSIONS: Our analysis does not show any difference in outcomes for patients treated with primary surgery or radiotherapy. Although the primary pattern of failure in both groups was distant metastatic disease, some local failures may be preventable with careful delineation of target volumes, especially near the base of skull region.

Free Thyroid Transfer: A Novel Procedure to Prevent Radiation-induced Hypothyroidism.

PURPOSE: The incidence of hypothyroidism after radiation therapy for head and neck cancer (HNC) has been found to be ≤53%. Medical treatment of hypothyroidism can be costly and difficult to titrate. The aim of the present study was to assess the feasibility of free thyroid transfer as a strategy for the prevention of radiation-induced damage to the thyroid gland during radiation therapy for HNC. METHODS AND MATERIALS: A prospective feasibility study was performed involving 10 patients with a new diagnosis of advanced HNC undergoing ablative surgery, radial forearm free-tissue transfer reconstruction, and postoperative adjuvant radiation therapy. During the neck dissection, hemithyroid dissection was completed with preservation of the thyroid arterial and venous supply for implantation into the donor forearm site. All patients underwent a diagnostic thyroid technetium scan 6 weeks and 12 months postoperatively to examine the functional integrity of the transferred thyroid tissue. RESULTS: Free thyroid transfer was executed in 9 of the 10 recruited patients with advanced HNC. The postoperative technetium scans demonstrated strong uptake of technetium at the forearm donor site at 6 weeks and 12 months for all 9 of the transplanted patients. CONCLUSIONS: The thyroid gland can be transferred as a microvascular free transfer with maintenance of function. This technique could represent a novel strategy for maintenance of thyroid function after head and neck irradiation.

Modification of the submandibular gland transfer procedure.

OBJECTIVES/HYPOTHESIS: The treatment for most advanced head and neck cancers (stage III and IV) usually includes radiation, and the most common side effect of this treatment modality is a permanent decrease in salivary production. Xerostomia is a devastating complication that significantly affects patients' quality of life by interfering with functions of taste, mastication, deglutition, and speech production. Treatment of xerostomia is varied, but one of the strategies developed by our group was to preserve one submandibular gland by surgically transferring it to the submental space and shielding it from the full dose of radiation. This procedure is proven to reduce the rate of radiation-induced xerostomia, but its main disadvantage is that it is contraindicated in oral cavity cancer. This study describes and evaluates a modification of the submandibular gland transfer (SGT) procedure, where the submandibular gland contralateral to the disease process is relocated to the parotid region. This modification has the potential of expanding the benefits of submandibular gland transfer procedures to patients with oral cavity cancers. STUDY DESIGN: Prospective feasibility study. METHODS: This study involved nine patients with a new diagnosis of advanced head and neck cancer undergoing major head and neck cancer resection with postoperative adjuvant radiation therapy. The new modified salivary gland transfer procedure was performed on all nine patients, and the glands total dose received with radiation therapy was assessed. RESULTS: All the modified SGT procedures were successful with no post-operative complications. The radiation oncology team has been able to successfully localize the transferred submandibular glands and shield them from the radiation beam postoperatively. CONCLUSIONS: We have successfully demonstrated that surgical transfer of a submandibular salivary gland to the parotid region is feasible, surgically viable, oncologically sound, and does not interfere with radiation therapy. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:2492-2496, 2016.

Making a case for high-volume robotic surgery centers: A cost-effectiveness analysis of transoral robotic surgery.

OBJECTIVE: To evaluate the cost-effectiveness of transoral robotic surgery (TORS) compared to intensity-modulated radiotherapy (IMRT) for early stage (T1-2, N0, M0) oropharyngeal squamous cell carcinoma (OPSCC). PATIENTS AND METHODS: A Markov decision tree model with a 5-year time horizon was developed. Comparative groups were: i) TORS with concurrent ipsilateral neck dissection +/- adjunctive IMRT, and ii) primary IMRT. Primary outcome was cost/quality adjusted life year (QALY). Perspective was the United States third party payer. Costs and effects were discounted at a rate of 3.5%. A threshold and probabilistic sensitivity analysis were performed. RESULTS: TORS strategy cost $30,992 and provided 4.81 QALYs/patient. The IMRT strategy cost $26,033 and provided a total of 4.78 QALYs/patient. The incremental cost effectiveness ratio for TORS vs. IMRT in the reference case was $165,300/QALY. The probability that TORS is cost-effective compared to IMRT at a maximum willingness-to-pay threshold of $50,000/QALY is 42%. CONCLUSION: An IMRT strategy for management of early stage OPSCC is more likely to be cost-effective compared to TORS. To improve the value of TORS for early stage OPSCC, consolidating TORS procedures to create high-volume centers of excellence may be a potential strategy to increase incremental effectiveness and reduce incremental costs. J. Surg. Oncol. 2015 111:155-163. © 2015 Wiley Periodicals, Inc.

A planning comparison of 3-dimensional conformal multiple static field, conformal arc, and volumetric modulated arc therapy for the delivery of stereotactic body radiotherapy for early stage lung cancer.

The primary objective of this study was to compare dosimetric variables as well as treatment times of multiple static fields (MSFs), conformal arcs (CAs), and volumetric modulated arc therapy (VMAT) techniques for the treatment of early stage lung cancer using stereotactic body radiotherapy (SBRT). Treatments of 23 patients previously treated with MSF of 48Gy to 95% of the planning target volume (PTV) in 4 fractions were replanned using CA and VMAT techniques. Dosimetric parameters of the Radiation Therapy Oncology Group (RTOG) 0915 trial were evaluated, along with the van׳t Riet conformation number (CN), monitor units (MUs), and actual and calculated treatment times. Paired t-tests for noninferiority were used to compare the 3 techniques. CA had significant dosimetric improvements over MSF for the ratio of the prescription isodose volume to PTV (R100%, p < 0.0001), the maximum dose 2cm away from the PTV (D2cm, p = 0.005), and van׳t Riet CN (p < 0.0001). CA was not statistically inferior to MSF for the 50% prescription isodose volume to PTV (R50%, p = 0.05). VMAT was significantly better than CA for R100% (p < 0.0001), R50% (p < 0.0001), D2cm (p = 0.006), and CN (p < 0.0001). CA plans had significantly shorter treatment times than those of VMAT (p < 0.0001). Both CA and VMAT planning showed significant dosimetric improvements and shorter treatment times over those of MSF. VMAT showed the most favorable dosimetry of all 3 techniques; however, the dosimetric effect of tumor motion was not evaluated. CA plans were significantly faster to treat, and minimize the interplay of tumor motion and dynamic multileaf collimator (MLC) motion effects. Given these results, CA has become the treatment technique of choice at our facility.

Nutrition impact symptoms in a population cohort of head and neck cancer patients: multivariate regression analysis of symptoms on oral intake, weight loss and survival.

OBJECTIVES: To evaluate the impact of 17 symptoms on reduced dietary intake, weight loss, and survival of patients with Head and Neck Cancer (HNC). METHODS: 635 Consecutive patients were screened (Patient- Generated Subjective Global Assessment©, Head and Neck Symptom Checklist©) before radiation and/or chemotherapy. Multivariate regression analyses were used to relate severity of symptoms to reduced dietary intake and weight loss and identify prognostic individual symptoms impact on dietary intake. Cox proportional hazards model was used to find significant predictors of survival. RESULTS: Aggregate burden of symptoms was a significant independent predictor of reduced intake, weight loss and survival. Patients with a highest total symptom scores survived significantly less (205days, 95% CI=146-264) compared to patients with lowest total symptom score (577days, CI=429-725), log-rank P<0.001). Loss of appetite, difficulty chewing, dry mouth, thick saliva and pain were individual symptoms that significantly associated with reduced dietary intake in the entire cohort. In subgroup analyses, tumor location, disease stage, performance status, and presence of dysphagia altered the profile of individual symptoms that predict intake. However across all subgroups loss of appetite had the highest impact (OR=4.6; 95% CI=3.1-6.8), followed by difficulty chewing (OR=2.5; 95% CI=2.0-3.9). CONCLUSION: HNC patients experience significant symptom burden prior to radiation and chemotherapy. The nutritional impact of these symptoms on dietary intake is revealed by multivariate analysis and support the suggestion that unique individual symptom profiles require management to improve nutritional status.

Primary surgery versus chemoradiotherapy for advanced oropharyngeal cancers: a longitudinal population study.

BACKGROUND: Treatment for advanced stage oropharyngeal squamous cell carcinoma (OPSCC) includes combined chemoradiation therapy or surgery followed by radiation therapy alone or in combination with chemotherapy. The goal of this study was to utilize available evidence to examine survival outcome differences in patients with advanced stage OPSCC treated with these different modalities. METHODS: Patients with advanced stage OPSCC were identified. Primary outcome measurements were disease specific and overall survival rates with differences examined via Kaplan-Meier and logistic regression analysis. RESULTS: 344 patients were enrolled. 94 patients underwent triple modality therapy inclusive of surgery followed by adjuvant combined chemotherapy and radiation therapy (S-CRT). 131 had surgery and radiation therapy (S-RT), while 56 had chemoradiation (CRT) therapy as their primary treatment. A total of 63 patients had single modality radiation therapy and were excluded from analysis due to the large number of palliative patients. Kaplan-Meier overall survival analysis showed that therapy with S-CRT had the highest disease specific survival at five years (71.1%). This is contrasted against S-RT and CRT, with five year survival rates at 53.9%, and 48.6%, respectively. Cox regression showed that the comparison of S-CRT vs. S-RT, and CRT is associated with statistically significant increased hazard ratios of 1.974, and 2.785, indicating that both S-RT and CRT are associated with a reduced likelihood of survival at 5 years when compared to S-CRT. CONCLUSIONS: In this population based cohort study S-CRT is associated with a 17-22% 5 year disease specific survival benefit compared to CRT or S-RT.

Clinical determinants of weight loss in patients receiving radiation and chemoirradiation for head and neck cancer: a prospective longitudinal view.

BACKGROUND: We aimed to determine the effects of systemic inflammation and symptoms of head and neck cancer patients on dietary intake and weight in relation to mode of treatment. METHODS: In all, 38 orally fed patients had intake, weight, C-reactive protein (CRP), and symptoms prospectively assessed at baseline, post-treatment, and follow-up. RESULTS: Intake/weight declined and CRP increased substantially in chemoirradiation patients (-11.4 ± 5.2 kg, -1214 kcal/day, 23.4 ± 24.9 mg/L; p < .05) versus radiotherapy patients (-3.5 ± 4.8 kg, -483 kcal/day, 8.3 ± 13.9 mg/L) during posttreatment (repeated-measures ANOVA). Multivariate generalized estimating equations modeling identified reduced swallowing capacity was a key predictor of energy intake in both treatment groups (p < .001); multiple symptoms experienced by radiotherapy/chemoirradiation patients were significant predictors of weight loss; additionally, in chemoirradiation patients, CRP was an independent predictor of weight loss (p < .001). CONCLUSIONS: Treatment of symptoms and systemic inflammation are important clinical targets to manage weight loss in patients with head and neck cancer, especially those treated with chemoirradiation.

Salivary gland sparing in the treatment of head and neck cancer.

Radiotherapy is an important component of the multimodality treatment of head and neck cancer. Although an effective treatment for many patients, it can have significant long-term sequelae. In particular, xerostomia - or dry mouth - caused by salivary gland injury is a serious problem suffered by most patients and leads to problems with oral comfort, dental health, speech and swallowing. This article explores the mechanisms behind radiation injury to the major salivary glands, as well as different strategies to minimize and alleviate xerostomia. This includes technical approaches to minimize radiation dose to salivary tissue, such as intensity-modulated radiotherapy and surgical transfer of salivary glands, as well as pharmacologic approaches to stimulate or protect the salivary tissue. The scientific literature will be critically examined to see what works and what strategies have been less effective in attempting to minimize xerostomia in head and neck cancer patients.

Dose-volume analysis of locoregional recurrences in head and neck IMRT, as determined by deformable registration: a prospective multi-institutional trial.

BACKGROUND AND PURPOSE: Although IMRT for head and neck cancer is widely accepted, the implications of sparing normal tissue immediately adjacent to target volumes are not well known. MATERIALS AND METHODS: Between 2002 and 2007, 124 patients with head and neck cancer were treated with surgery and postoperative IMRT (n=79) or definitive RT (n=45). Locoregional recurrences were analyzed for location relative to target volumes, and dosimetry. RESULTS: With a median follow-up of 26.1months, a total of 16 locoregional recurrences were observed. The five-year actuarial locoregional disease-free survival was 82% [95% CI, 72-90%]. Analysis of 18 distinct sites of locoregional failure revealed that five of these failures were within the high dose clinical target volume (CTV), nine failures were at the margin of the CTV, and four recurrences were outside the CTV. The mean dose delivered to these recurrent volumes was 63.1 Gy [range: 57-68 Gy], while the mean dose to the coolest 1cc within each recurrence was 60.0 Gy [range: 51-67 Gy]. There were two periparotid recurrences observed. CONCLUSIONS: We observed excellent locoregional control rates overall. The majority of recurrences occur within high dose regions of the neck and not near the spared parotid glands.

Prognostic factors for complete obliteration of arteriovenous malformations treated with LINAC-based stereotactic radiosurgery.

OBJECTIVES: Few series analyzing prognostic fac tors predicting for obliteration of arteriovenous malformations (AVMs) following linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) have been reported. We analyzed prognostic variables, outcomes, and toxicities in 88 patients undergoing LINAC-based SRS for AVMs. METHODS: Following IRB approval, patient records were retrospectively analyzed to identify independent predictors of complete response (obliteration) (CR) and time-to-CR. The majority of AVMs were treated using multiple isocenters and non-coplanar arcs. The median AVM volume was 2.67 cm3 (0.05 - 33.51). Median marginal and maximal doses were 17 (12-24) and 26.1 Gy (15-40), with a median prescription isodose surface of 65%. RESULTS: Spetzler-Martin (SM) grade was determined for 86 patients and was: I-3 pts (3%); II-23 pts (27%); III-45 pts (52%); IV-13 pts (15%); V-2 pts (2%).Of 80 patients with follow-up imaging, 44 (55%) had documented complete responses (CR). Kaplan-Meier estimate probability for CR at 4 years was 62% (95% CI: 0.50, 0.74). Median time to CR was 3 years (95% CI: 2.08, 3.17). Multivariate analysis demonstrated the Spetzler-Martin grade (OR=0.14 for grade III vs. grade I-II; p=0.004 and OR 0.07 for grade IV-V vs. grade I-II; p=0.002) and dichotomized marginal dose > 17 Gy (OR=4.19; p=0.01) to be significantly associated with CR. DISCUSSION: This report demonstrates that for LINAC-based SRS of AVM, marginal dose and Spetzler-Martin grade are strong predictors of complete AVM obliteration.