Five-year outcomes of an oropharynx-directed treatment approach for unknown primary of the head and neck.

PURPOSE: Squamous cell carcinoma of unknown primary (SCCHNUP) is commonly treated with comprehensive radiation to the laryngopharynx and bilateral necks. In 1998, we established a departmental policy to treat SCCHNUP with radiation directed to the oropharynx and bilateral neck. METHODS: From 1998-2011, 60 patients were treated - N1: 18%, N2: 75% and N3: 7%. 82% underwent neck dissection. 55% received IMRT and 62% underwent concurrent chemoradiotherapy. RESULTS: At median follow-up of 54months, 5 patients failed regionally and 4 emerged with a primary (tongue base, hypopharynx and thoracic esophagus). Five-year rates of regional control, primary emergence, distant metastasis, disease-free survival and overall survival were 90%, 10%, 20%, 72% and 79%, respectively. The 5year rate of primary emergence in a non-oropharynx site was 3%. CONCLUSION: This is the first demonstration that an oropharynx-directed approach yields low rates of primary emergence in SCCHNUP with excellent oncologic outcomes.

Low rates of contralateral neck failure in unilaterally treated oropharyngeal squamous cell carcinoma with prospectively defined criteria of lateralization.

BACKGROUND: Unilateral radiotherapy (RT) of oropharyngeal carcinomas is accepted for patients with lateralized primary and low-volume nodal disease. Utilizing prospectively defined criteria of laterality and staging positron emission tomography (PET)/CT, we studied outcomes in patients with advanced-stage oropharyngeal cancer undergoing unilateral RT. METHODS: Thirty-seven patients with oropharyngeal tumors >1 cm from midline regardless of node status underwent unilateral RT and were followed prospectively. Patient characteristics: T1 = 11; T2 = 22; T3 = 4; N0 = 3; N1 = 9; N2a = 3; N2b = 21; and Nx = 1. Dosimetry were determined and weekly National Comprehensive Cancer Network (NCCN) distress thermometer data were collected. RESULTS: At median follow-up of 32 months, 3-year locoregional control, contralateral regional failure, distant metastasis-free survival, and disease-free survival were 96%, 0%, 7%, and 93%, respectively. CONCLUSION: Low rates of contralateral neck failure are demonstrated utilizing prospectively defined criteria for unilateral RT. The tolerances of contralateral organs are respected and patients report low to moderate levels of distress throughout treatment.

State-of-the-art management of renal cell carcinoma.

In the United States, renal cell cancer (RCC) is the third most common genitourinary tumor and the seventh most common cancer. Standard treatment of the primary tumor in RCC is complete resection by either a radical or partial nephrectomy which can be done as an open procedure or laparoscopically. Given the increasing incidence in the diagnosis of early-stage RCC and the toxicity and invasiveness associated with surgery, less invasive options (eg, radiofrequency ablation) have been used recently as an alternative. Although conventional radiotherapy plays a role in the palliative setting, its role is otherwise limited. This is partly because of the in vitro and clinical data showing that RCC is relatively radioresistant to radiotherapy. The advances in immobilization and image guidance have led several investigators to consider stereotactic techniques to overcome this resistance with impressive results in the metastatic setting. Recent retrospective and prospective phase II trials of RCC stereotactic body radiotherapy have shown excellent local controls up to 90% to 98%. Given these results and the noninvasive nature of stereotactic body radiotherapy this modality should be further evaluated as a treatment of choice for the primary RCC tumor. Although RCC is also resistant of conventional chemotherapy agents, exciting recent advances have emerged in the treatment of systemic disease with the development of targeted agents in addition to immunotherapy-based treatments. In the current critical review we discuss these emerging trends in localized and systemic treatment as well as possible interesting combinations of the 2 modalities.

Long-term follow-up and pattern of failure for T1-T2 glottic cancer after definitive radiation therapy.

PURPOSE: To evaluate the impact of radiation therapy (RT) on the long-term outcomes and pattern of failure for T1-2 glottic cancer. MATERIALS AND METHODS: This is a single-institution, retrospective study. From January (1997 to 2010), 253 patients with early glottic cancer underwent RT by 2-dimensional or 3-dimensional RT with Co or linear accelerator. Appropriate daily bolus was applied with linear accelerator-based RT to avoid under dosage of the anterior commissure. RESULTS: A total of 253 patients with T1-T2 glottic cancer were treated with definitive RT. The median age was 65 and males made up 87% of the population. T1 was 77% of the population. The median dose and fraction size were 63 and 2.25 Gy, respectively. After a median follow-up of 83 months, the locoregional control (LRC) for the whole cohort was 98%. Specifically, LRCs for T1 (195 patients) and T2 (58 patients) were 99.5% and 91%, respectively. Kaplan-Meier curve shows the 5-year cause-specific survival to be 100%. CONCLUSIONS: Single-modality RT provides an excellent and effective treatment for T1-T2 glottic cancer with remarkable functional preservation and 5-year LRC of 98% with negligible long-term toxicity.

Integrating innovative therapeutic strategies into the management of renal cell carcinoma.

Three emerging trends have occurred recently in renal cell carcinoma (RCC). First, over the last several decades there has been a marked increase in the diagnosis of RCC, with a corresponding decrease in the typical tumor size, resulting in an increased interest in less invasive approaches to primary tumor treatment. Second, while conventional radiotherapy plays a limited palliative role due to the relative radio-resistance of RCC, advances in immobilization and image guidance have led several investigators to consider stereotactic radiotherapy techniques (SRT) to overcome this resistance, with impressive results in the metastatic setting. In addition, preliminary use of SRT to treat the primary RCC tumor is underway. Thirdly, although RCC is resistant to conventional chemotherapy agents, exciting recent advances have emerged in the treatment of clear cell RCC, with the development of targeted agents in addition to immunotherapy-based treatments. In the current critical review we discuss these emerging trends in localized and systemic treatment as well as possible interesting combinations of the two modalities. Finally, we discuss the role of the new systemic agents in non-clear cell RCC.

The impact of body mass index on heterotopic ossification.

PURPOSE: To analyze the impact of different body mass index (BMI) as a surrogate marker for heterotopic ossification (HO) in patients who underwent surgical repair (SR) for displaced acetabular fractures (DAF) followed by radiation therapy (RT). METHODS AND MATERIALS: This is a single-institution retrospective study of 395 patients. All patients underwent SR for DAF followed by RT ± indomethacin. All patients received postoperative RT, 7 Gy, within 72 h. The patients were separated into four groups based on their BMI: <18.5, 18.5-24.9, 25-29.9, and >30. The end point of this study was to evaluate the efficacy of RT ± indomethacin in preventing HO in patients with different BMI. RESULTS: Analysis of BMI showed an increasing incidence of HO with increasing BMI: <18.5, (0%) 0/6 patients; 18.5-24.9 (6%), 6 of 105 patients developed HO; 25-29.9 (19%), 22 of 117; >30 (31%), 51 of 167. Chi-square and multivariate logistic regression analysis showed that the correlation between odds of HO and BMI is significant, p < 0.0001. As the BMI increased, the risk of HO and Brooker Classes 3, 4 HO increased. The risk of developing HO is 1.0× (10%) more likely among those with higher BMI compared with those with lower BMI. For a one-unit increase in BMI the log odds of HO increases by 1.0, 95% CI (1.06-1.14). Chi-square test shows no significant difference among all other factors and HO (e.g., indomethacin, race, gender). CONCLUSIONS: Despite similar surgical treatment and prophylactic measures (RT ± indomethacin), the risk of HO appears to significantly increase in patients with higher BMI after DAF. Higher single-fraction doses or multiple fractions and/or combination therapy with nonsteroidal inflammatory drugs may be of greater benefit to these patients.

The impact of class III (morbid) obesity on heterotopic ossification outcomes.

PURPOSE: Obesity is associated with a chronic low inflammatory process that may act as common soil for the pathogenesis of obesity-related comorbidities including heterotopic ossification (HO). The purpose of this study is to compare the incidence of HO between patients with body mass index (BMI) <40 versus ≥40 after operative treatment of displaced acetabular fractures followed by radiation therapy (RT) ± indomethacin. METHODS AND MATERIALS: This is a single institution retrospective chart review of 419 patients. All patients with well-documented BMI underwent operative treatment followed by RT ± indomethacin. All patients received 700 cGy to the soft tissues around the proximal femur and acetabulum without bone shielding. All RT were given postoperatively within 72 hours. The patients were divided into 2 groups: Group (A) BMI < 40 and Group (B) BMI ≥40. HO was assessed with X-ray. BMI was used as a surrogate measure to test the risk of HO despite prophylaxis. RESULTS: The incidence of HO among all patients is 21% (89 of 419), while among those in group A (BMI <40), 68 of 374 patients developed HO (18%); in the morbidly obese group (BMI ≥40) 21of 45 patients developed HO (47%). The difference between the rates of HO in the 2 groups was 29%; the χ(2) test showed a significant difference between the 2 BMI groups (P < .001 at α = 0.05). CONCLUSIONS: There is a higher incidence of HO among the morbidly obese patients despite RT ± indomethacin. RT doses for HO prophylaxis in morbidly obese patients need to be reassessed; also, understanding the signaling pathways in target tissues in obese patients at which adipokines control metabolism may reveal novel therapies. Higher radiation doses ± indomethacin may need to be considered and optimally evaluated in the context of a prospective, randomized clinical trial.