Diane C. Ling

Postoperative stereotactic radiosurgery to the resection cavity for large brain metastases: clinical outcomes, predictors of intracranial failure, and implications for optimal patient selection.

BACKGROUND Postoperative stereotactic radiosurgery for brain metastases potentially offers similar local control rates and fewer long-term neurocognitive sequelae compared to whole brain radiation therapy, although patients remain at risk for distant brain failure (DBF). OBJECTIVE To describe clinical outcomes of adjuvant stereotactic radiosurgery for large brain metastases and identify predictors of intracranial failure and their implications on optimal patient selection criteria. METHODS We performed a retrospective review on 100 large (>3 cm) brain metastases in 99 patients managed by resection followed by postoperative stereotactic radiosurgery to a median dose of 22 Gy (range, 10-28) in 1 to 5 fractions (median, 3). Primary histology was nonsmall cell lung in 40%, breast cancer in 18%, and melanoma in 17%. Forty (40%) patients had uncontrolled systemic disease. RESULTS With a median follow-up of 12.2 months (range, 0.6-87.4), the 1-year Kaplan-Meier local control was 72%, DBF 64%, and overall survival 55%. Nine patients (9%) developed evidence of radiation injury, and 6 (6%) developed leptomeningeal disease. Uncontrolled systemic disease (P=.03), melanoma histology (P=.04), and increasing number of brain metastases (P<.001) were significant predictors of DBF on Cox multivariate analysis. Patients with <4 metastases, controlled systemic disease, and nonmelanoma primary (n=47) had a 1-year DBF of 48.6% vs 80.1% for all others (P=.01). CONCLUSION Postoperative stereotactic radiosurgery to the resection cavity safely and effectively augments local control of large brain metastases. Patients with <4 metastases and controlled systemic disease have significantly lower rates of DBF and are ideal treatment candidates.

Oncologic outcomes and patient-reported quality of life in patients with oropharyngeal squamous cell carcinoma treated with definitive transoral robotic surgery versus definitive chemoradiation

OBJECTIVE It has been postulated that treatment outcomes are similar between transoral robotic surgery (TORS) and definitive chemoradiation (CRT) for oropharyngeal squamous cell carcinomas (OPSCC). We compared oncologic and quality of life (QOL) outcomes between definitive CRT and definitive TORS. MATERIALS AND METHODS An observational comparison study was performed on 92 patients treated with TORS±adjuvant therapy and 46 patients treated with definitive CRT between July 2005 and January 2016. The Kaplan Meier method was used for survival analyses, and the Mann-Whitney test was used to compare QOL scores between groups. RESULTS All patients had T0-T2 and N0-N2 disease, although CRT patients had higher clinical staging (p<0.001). HPV+ disease was present in 79% (n=73) of TORS patients and 91% (n=19) of tested CRT patients. Median follow-up was 22.1months (range: 0.33-83.4). There were no significant differences in locoregional control or overall survival between CRT and TORS groups. Definitive TORS resulted in better saliva-related QOL than definitive CRT at 1, 6, 12, and 24months (p<0.001, p=0.025, p=0.017, p=0.011). Among TORS patients, adjuvant therapy was associated with worse QOL in the saliva domain at 6, 12, and 24months (p<0.001, p<0.001, p=0.007), and taste domain at 6 and 12months (p=0.067, p=0.008). CONCLUSION Definitive CRT and definitive TORS offer similar rates of locoregional control, overall survival, and disease-free survival in patients with early stage OPSCC. TORS resulted in significantly better short and long-term saliva-related QOL, whereas adjuvant therapy was associated with worse saliva and taste-related QOL compared to TORS alone.

Incidence of hospitalization in patients with head and neck cancer treated with intensity‐modulated radiation therapy

Patients with primary head and neck cancer managed with radiation therapy (RT) +/‐ chemotherapy may experience significant treatment‐related toxicities. We assessed hospitalization as a metric for severe treatment‐related toxicities and evaluated patient and treatment factors for possible association.

Underutilization of radiation therapy in early-stage marginal zone lymphoma negatively impacts overall survival.

PURPOSE Multiple population-based studies have suggested increasing omission of radiation therapy in favor of alternative treatment strategies in lymphomas, with an associated negative impact on survival. Radiation therapy has long been considered the standard management for many mucosa-associated lymphoid tissue lymphomas. Thus, we aimed to evaluate patterns of treatment utilization and survival. METHODS AND MATERIALS A retrospective analysis based on the National Cancer Database was performed on 22,378 patients with splenic, nodal, or extranodal stage I-II marginal zone lymphoma diagnosed between 1998 and 2012. A logistic regression model was used to assess the association between sociodemographic, tumor, and treatment characteristics and the utilization of radiation therapy. Multivariate propensity score-adjusted Cox proportional hazards models were performed to identify factors independently associated with overall survival (OS). RESULTS Of 22,378 patients, 82% had stage I disease, 77% had extranodal mucosa-associated lymphoid tissue lymphoma, 5% had splenic marginal zone lymphoma, and 64% were older than 60 years. Radiation therapy utilization decreased from a peak of 39% in 2007 to 33% in 2011 (P < .001), with a corresponding significant increase in systemic therapy utilization. Radiation therapy was associated with a 5- and 10-year OS of 86.7% and 68.8% compared with 78.3% and 54.3% for no radiation therapy (P < .001). On multivariate propensity score-adjusted survival analysis, radiation therapy remained independently associated with improved OS (hazard of death, 0.75; 95% confidence interval, 0.65-0.85; P < .001). CONCLUSIONS Although clinical guidelines endorse radiation therapy as the preferred initial therapy for early-stage nongastric and Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma, radiation therapy is underused. Radiation therapy with or without systemic therapy was associated with a significant improvement in OS and should remain standard of care.

Locoregional Recurrent or Second Primary Head and Neck Cancer: Management Strategies and Challenges.

Treatment of patients with locoregional recurrent or second primary head and neck squamous cell cancer (HNSCC) has been guided by well-reasoned principles and informed by carefully tested chemotherapy and radiation regimens. However, clinical decision making for this population is complicated by many factors. Although surgery is generally considered the treatment of choice for patients with HNSCC with recurrent disease or new second primary disease in a previously irradiated field, operability of cases is not always straightforward. Postoperative treatment is frequently warranted but carries significant risk. In addition, the rapid rise in the incidence of HPV-associated HNSCC raises the question of whether established treatment paradigms should be re-examined in this population of patients with a much better prognosis than the non-HPV population. Furthermore, new radiation techniques and new systemic agents show early promising results in recent clinical studies, suggesting potential for practice-changing effects in the future management of this disease. This article examines each of the treatment modalities used in the care of patients with HNSCC with recurrent or new second primary disease and provides a perspective to aid clinicians in the management of this disease.

Role of Immunotherapy in Head and Neck Cancer

Immune system dysfunction plays a role in both the development and progression of head and neck squamous cell carcinoma (HNSCC), highlighting the potential role for immunotherapy to improve outcomes in this disease. The application of anti-PD-1 therapies for recurrent or metastatic HNSCC has found promising results. This has led to interest in combining immunotherapy with radiation therapy (RT) for the primary treatment of locally advanced HNSCC. RT with concurrent cetuximab is an option for patients who are medically unfit to receive cisplatin, and ongoing trials seek to determine to role of cetuximab-RT in treatment de-intensification for HPV+ oropharyngeal HNSCC. Other ongoing trials are evaluating the use of anti-PD-1 and anti-PD-L1 therapies in the upfront setting for newly diagnosed high-risk, locally advanced HNSCC, in an effort to improve disease control. Finally, early phase I studies are now investigating the use of anti-PD-1 therapy in conjunction with RT for refractory recurrent or metastatic HNSCC.

Stereotactic Body Radiation Therapy for Recurrent Head and Neck Cancer.

AbstractStereotactic body radiation therapy (SBRT) offers a promising opportunity for cure and/or palliation to patients with recurrent head and neck cancer whose comorbidities, performance status, and history of prior treatment may preclude many other salvage options. Stereotactic body radiation therapy appears to have a favorable response and toxicity profile compared with other nonoperative salvage options for recurrent head and neck cancer. However, the risk of severe toxicity remains, with carotid blowout syndrome a unique concern, although the incidence of this complication may be minimized with alternating-day fractionation. The short overall treatment time and low rates of acute toxicity make SBRT an optimal vehicle to integrate with novel systemic therapies, and several phase II studies have used concurrent cetuximab as a radiosensitizer with SBRT with promising results. Ongoing studies aim to evaluate the potential synergistic effect of SBRT with immune checkpoint inhibitors in recurrent head and neck cancer.

Oncologic Outcomes in Patients with Oropharyngeal Squamous Cell Carcinoma Treated with TORS versus Definitive CRT

Objectives: It has been postulated that treatment outcomes are similar between transoral robotic surgery (TORS) and definitive chemoradiation (CRT) for patients with oropharyngeal squamous cell carcinomas (OPSCC). We compared oncologic outcomes between OPSCC patients treated with definitive CRT and those treated with TORS only. Methods: An observational comparison study was performed on 23 patients treated with TORS without adjuvant therapy and 33 patients treated with definitive CRT between July 2005 and December 2013. All patients had early stage disease with T0-T2 and N0-N2. Median age was 57 (range: 36-82) years and 80.4% of patients were male, which was similar between groups. Human papillomavirus (HPV)+ disease was present in 70.0% of TORS and 33.3% of CRT patients, although HPV status was not tested in 63.6% of the CRT patients. Results: Median follow-up was 22.5 months (range, 0.33-83.4 months). Local failure rate for the entire cohort was 7.1% (9.1% for definitive CRT, 4.3% for TORS, P = .85). Overall regional failure rate was 3.6% (3.0% for definitive CRT, 4.3% for TORS, P = .48). Overall distant failure rate was 5.4% (9.1% for definitive CRT, 0.0% for TORS, P = .24). Two-year actuarial disease-free survival (DFS) was 86.7% for definitive CRT patients and 80.0% for patients treated with TORS alone (P = .69). Conclusions: Definitive CRT and TORS alone offer similar rates of locoregional control, distant control, and DFS in patients with early stage OPSCC. Further studies are needed to assess the effect of CRT and TORS on quality of life in this patient population.