Faculty Bibliography

BACKGROUND:Previous groups have shown contralateral submandibular gland sparing to improve xerostomia with safe outcomes, but primarily in early-stage disease. In this study, we present a large cohort of patients with locally advanced head and neck cancer that underwent contralateral submandibular gland-sparing radiotherapy, to demonstrate feasibility and safety specifically in patients with locally advanced disease. METHODS:We retrospectively analyzed patients who were treated prospectively with contralateral submandibular gland sparing. Only patients who underwent bilateral neck radiotherapy with contralateral submandibular gland doses <39 Gy were included. RESULTS:We identified 71 patients. Approximately 80% of patients had ≥N2b disease. The contralateral submandibular gland mean dose was 33 Gy and, at a median follow-up of 27.3 months, no patients experienced treatment failure in the contralateral level IB lymph nodes. CONCLUSION/CONCLUSIONS:Xerostomia remains a significant morbidity despite parotid sparing and can be minimized further by contralateral submandibular gland sparing. These data provide important preliminary evidence that contralateral submandibular gland sparing is feasible and may be safe even in locally advanced cancers.

BACKGROUND:To investigate the dose-volume factors in mastication muscles that are implicated as possible causes of trismus in patients following treatment with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy for head and neck cancers. MATERIAL AND METHODS/METHODS:All evaluable patients treated at our institution between January 2004 and April 2009 with chemotherapy and IMRT for squamous cell cancers of the oropharynx, nasopharynx, hypopharynx or larynx were included in this analysis (N = 421). Trismus was assessed using CTCAE 4.0. Bi-lateral masseter, temporalis, lateral pterygoid and medial pterygoid muscles were delineated on axial computed tomography (CT) treatment planning images, and dose-volume parameters were extracted to investigate univariate and multimetric correlations. RESULTS:Forty-six patients (10.9%) were observed to have chronic trismus of grade 1 or greater. From analysis of baseline patient characteristics, toxicity correlated with primary site and patient age. From dose-volume analysis, the steepest dose thresholds and highest correlations were seen for mean dose to ipsilateral masseter (Spearman's rank correlation coefficient Rs = 0.25) and medial pterygoid (Rs = 0.23) muscles. Lyman-Kutcher-Burman modeling showed highest correlations for the same muscles. The best correlation for multimetric logistic regression modeling was with V68Gy to the ipsilateral medial pterygoid (Rs = 0.29). CONCLUSION/CONCLUSIONS:Chemoradiation-induced trismus remains a problem particularly for patients with oropharyngeal carcinoma. Strong dose-volume correlations support the hypothesis that limiting dose to the ipsilateral masseter muscle and, in particular, the medial pterygoid muscle may reduce the likelihood of trismus.

OBJECTIVES/OBJECTIVE:To assess whether sparing neck-level IB in target delineation of node-positive (N+) oropharyngeal carcinoma (OPC) can improve xerostomia outcomes without compromising locoregional control (LRC). METHODS:A total of 125 N+ OPC patients with a median age of 57 years underwent chemoradiation between May 2010 and December 2011. A total of 74% of patients had T1-T2 disease, 26% T3-T4, 16% N1, 8% N2A, 48% N2B, 28% N2C; 53% base of tongue, 41% tonsil, and 6% other. Patients were divided into those who had target delineation sparing of bilateral level IB (the spared cohort) versus no sparing (the treated cohort). Sparing of contralateral high-level II nodes was also performed more consistently in the spared cohort. A prospective xerostomia questionnaire (patient reported) was given at each patient follow-up visit to this cohort of patients to assess late xerostomia. Clinical assessment (observer rated) at each patient follow-up visit was also recorded. RESULTS:The 2-year LRC for the spared and treated cohorts was 97.5% and 93.8%, respectively (median follow-up, 23.2 mo). No locoregional failures occurred outside of treatment fields. The spared cohort experienced significant benefits in patient-reported xerostomia summary scores (P=0.021) and observer-rated xerostomia scores (P=0.006). In addition, there were significant reductions in mean doses to the ipsilateral submandibular gland (63.9 vs. 70.5 Gy; P<0.001), contralateral submandibular gland (45.0 vs. 56.2 Gy; P<0.001), oral cavity (35.9 vs. 45.2 Gy; P<0.001), and contralateral parotid gland (20.0 vs. 24.4 Gy; P<0.001). CONCLUSIONS:Target delineation sparing of bilateral level IB nodes in N+ OPC reduced mean doses to salivary organs without compromising LRC. Patients with reduced target volumes had better patient-reported xerostomia outcomes.

INTRODUCTION: We expanded upon our previous experience using involved-field fractionated radiotherapy (IFRT) as an alternative to whole brain radiotherapy or stereotactic radiosurgery for patients with surgically resected brain metastases (BM). MATERIALS AND METHODS: All patients with single BM who underwent surgical resection followed by IFRT at our institution from 2006 to 2013 were evaluated. Local recurrence (LR)-free survival, distant failure (DF)-free survival, and overall survival (OS) were determined. Analyses were performed associating clinical variables with LR and DF. Salvage approaches and toxicity of treatment for each patient were also assessed. RESULTS: Median follow-up was 19.1 months. Fifty-six patients were treated with a median dose of 40.05 Gy/15 fractions with IFRT to the resection cavity. LR-free survival was 91.4%, DF-free survival was 68.4%, and OS was 77.7% at 12 months. No variables were associated with increased LR; however, melanoma histopathology and infratentorial location were associated with DF on multivariate analysis. LRs were salvaged in 5/8 patients, and DFs were salvaged in 24/29 patients. Two patients developed radionecrosis. CONCLUSION: Adjuvant IFRT is feasible and safe for well-selected patients with surgically resected single BM. Acceptable rates of local control and salvage of distal intracranial recurrences continue to be achieved with continued follow-up.

PURPOSE/OBJECTIVE:We sought to identify risk factors for distant metastasis (DM) in patients with oropharyngeal cancer (OPC) and perform a recursive partition analysis (RPA) to identify patients both at low and high risk for DM. METHODS:Our center treated 647 consecutive OPC patients with IMRT between 9/98 and 1/12. The following clinical features were used as prognostic factors: T Stage, N Stage, smoking history, tumor grade, tumor sub-site, the presence of a low lying (level IV or VB) lymph node (LLLN). A Cox model of the risk of DM was used to identify independent prognostic factors. RPA was used to identify patients at low, intermediate, and high risk for DM. RESULTS:The median follow-up time in living patients was 42.2months (range: 2-166). The primary OPC site was the tonsil in 296 patients, base of tongue in 315 patients, and soft palate or pharyngeal wall in 36 patients. For the entire cohort, the Kaplan-Meier estimate for 3year freedom from distant metastasis was 88.4%. A Cox model identified T Stage (p<0.001), N Stage (p=0.02), and LLLN (p=0.002) as independent predictors of DM. RPA identified patients at low, intermediate, and high risk of DM, with a 3-year freedom-from DM of 98%, 91.1%, and 65.4% respectively. CONCLUSION/CONCLUSIONS:The presence of a low lying lymph node is significantly associated with an increased risk of DM in OPC. RPA identified patients both at very low and very high risk for DM with information routinely obtained in clinic.

OBJECT/OBJECTIVE:Radiation therapy is known to impair wound healing. Higher dose per fraction is believed to increase this risk. This study sought to quantify rates of wound complication in patients receiving preoperative conventionally fractionated radiotherapy (XRT) or high-dose hypofractionated image-guided radiation therapy (IGRT) for spinal metastasis, and to identify predictors of wound complication. METHODS:The records of 165 consecutive patients who underwent spine surgery for metastasis at Memorial Sloan-Kettering Cancer Center between 1999 and 2010, with a history of prior radiation therapy, were reviewed. Patients with primary spine tumors, 2 courses of prior radiation therapy to the surgical site, total dose < 9 Gy, or radiation therapy adjacent to or partially overlapping the surgical site, were excluded. One hundred thirty patients received XRT (≤ 3 Gy/fraction) and 35 received IGRT (> 3 Gy/fraction). The total dose prescribed to the 100% isodose line to treat the planning target volume was 18-30 Gy in 1-5 fractions. Clinical factors evaluated included age, Karnofsky Performance Scale score, body mass index, presence of diabetes, smoking, ambulatory status, prior surgery at same spinal site, preoperative laboratory results (hemoglobin, lymphocyte count, and albumin), perioperative chemotherapy or steroids, estimated blood loss, extent of stabilization hardware, time between radiation therapy and surgery, number of vertebral bodies irradiated, total radiation dose, and dose per fraction of radiation therapy. Wound complication was defined as poor healing, dehiscence, or infection. Potential predictors of wound complication were assessed by univariate analyses using competing-risk methods to adjust for risk of death. results: For XRT patients, median dose was 30 Gy (range 11.5-70 Gy) with 72% of them receiving 3 Gy × 10 fractions. For IGRT patients, 66% received 18-24 Gy × 1 fraction and 23% received 6 Gy × 5 fractions. Groups differed only by the mean number of vertebral bodies treated (4.6 XRT and 1.8 IGRT, p < 0.0001). Wound complications occurred at a median of 0.95 months (range 0.4-3.9 months). A total of 22 wound events occurred in the XRT group and 2 in the IGRT group. The 6-month cumulative incidence of wound complications for XRT was 17% and for IGRT was 6%. There was no significant difference in wound complications between groups (IGRT vs XRT: hazard ratio 0.31, 95% CI 0.08-1.3; p = 0.11). Higher dose per fraction appeared to be associated with a lower risk of wound complication (hazard ratio 0.27, 95% CI 0.06-1.15; p = 0.08), which trended toward significance. Univariate analyses did not reveal any significant predictors of wound complications. CONCLUSIONS:Patients who underwent XRT or IGRT did not have significantly different rates of postoperative wound complications. This finding may be explained by the treatment of fewer vertebral bodies in IGRT patients, or by the low overall number of total events. With a wound complication rate of 6%, preoperative IGRT, a highly conformal treatment, resulted in a very low rate of surgical wound complication.

BACKGROUND:The results of RTOG-MRC randomized trial of photon (n=15) versus neutron (n=17) therapy in the 1980's reported an improved local control (LC) with neutron radiotherapy for unresectable salivary gland tumors. Due to increased severe toxicity with neutron radiotherapy and the paucity of neutron-therapy centers, we analyzed our institution's results of photon radiotherapy for unresectable salivary gland tumors. PATIENTS AND METHODS/METHODS:From 1990 to 2009, 27 patients with unresectable salivary gland cancer underwent definitive photon radiotherapy at our institution. Nodal involvement on presentation was found in 9 patients. Median dose of radiotherapy was 70 Gy. Chemotherapy was given to 18 patients, most being platinum-based regimens. Local control (LC), locoregional control (LRC), distant metastasis-free survival (DMFS), overall survival (OS), and toxicity outcomes were assessed. RESULTS:With a median follow-up of 52.4 months, the 2/5-year actuarial LC was 69% (95%CI ± 21.0%)/55% (± 24.2%), LRC was 65% (± 21.4%)/47% (± 21.6%), and DMFS was 71% (± 21.8%)/51% (± 22.8%), respectively using competing risk analysis. The median OS was 25.7 months, and the 2/5-year OS rates were 50% (± 19.0%)/29% (± 16.6%), respectively. Higher histologic grade was significant for an increased rate of DM (intermediate grade vs. low grade, p=0.04, HR 7.93; high grade vs. low grade, p=0.01, HR 13.50). Thirteen (48%) patient's experienced acute grade 3 toxicity. Late grade 3 toxicity occurred in three (11%) patients. CONCLUSIONS:Our data compares favorably to neutron radiotherapy with fewer late complications. Photon radiotherapy is an acceptable alternative to neutron radiotherapy in patients who present with unresectable salivary gland tumors.

HER2-positive breast cancer is a known risk factor for CNS metastases, and the use of trastuzumab in the adjuvant setting does not prevent brain metastases. The purpose of this study is to compare outcomes in HER2-positive and HER2-negative intracranial disease treated with stereotactic radiosurgery (SRS). Among 57 breast cancer patients with brain metastases, 28 patients were HER2-positive. All patients were treated with SRS as their first treatment modality for CNS metastases. The median dose was 20 Gy (range 12-20 Gy). Statistical analysis was performed using the Kaplan-Meier method and chi (2) test. With a median follow-up of 11.0 months, the median time to progression in the HER2-positive group compared with the HER2-negative group was 7 versus 11 months (p = 0.080), respectively. Salvage therapy was performed in 50 % of HER2-positive patients compared with 21 % of HER2-negative patients (p = 0.02). The median OS for the HER2-positive group compared with the HER2-negative group was 22 versus 12 months (p = 0.053). Stereotactic radiosurgery results in excellent local control in the treatment for breast cancer brain metastases. Compared with HER2-negative disease, HER2-positive disease appears to show higher rates of intracranial relapse despite better overall survival rates. This data suggests that we need effective adjuvant therapy to prevent and treat brain metastases in HER2-positive patients.