The Role of Radiotherapy for Meningeal Melanocytomas - A 20 Year Update.

BACKGROUND/AIM: Meningeal melanocytomas are rare tumors of the central nervous system and optimal treatment needs further clarification. This study compared subtotal resection (STR), STR plus radiation therapy (RT), gross total resection (GTR), and GTR+RT to better define the role of postoperative RT. PATIENTS AND METHODS: All cases reported in the literature were reviewed. Patients (n=184) with complete data were analyzed for local control (LC) and overall survival (OS). RESULTS: On univariate analysis, GTR (vs. STR) was associated with improved LC (p=0.016). When comparing the treatment regimens, best and worst results were found after GTR+RT and STR alone, respectively (p<0.001). On univariate analysis, GTR resulted in better OS than STR (p=0.041). Moreover, the treatment regimen had a significant impact on OS (p=0.049). On multivariate analyses of LC and OS, extent of resection and treatment regimen were found to be significant factors. After STR, RT significantly improved LC but not OS. After GTR, RT did not significantly improve LC or OS. CONCLUSION: GTR was significantly superior to STR regarding LC and OS. STR+RT resulted in significantly better LC when compared to STR alone.

Clinical outcomes following observation, post-operative radiation therapy, or post-operative chemoradiation for HPV-associated oropharyngeal squamous cell carcinomas.

BACKGROUND: Intermediate and high-risk features (IRFs/HRFs) for locoregional recurrence following initial surgery for oropharyngeal SCCs (OP-SCCs) were defined prior to the known association of HPV with OP-SCC. There are limited reports on practice patterns and outcomes associated with post-operative radiation therapy (PORT) or chemoradiation (POCRT) for HPV-associated OP-SCCs. MATERIALS/METHODS: The National Cancer Database was queried for patients with HPV-associated OP-SCCs managed initially with surgery with IRFs or HRFs. IRFs were defined as pT3/T4 disease, pN1-3 disease, and lymphovascular space invasion, and HRFs as positive margins and extranodal extension (ENE). Patients were stratified into no adjuvant therapy, PORT, or POCRT arms. Kaplan-Meier analysis was utilized for comparison of overall survival (OS) between treatment arms followed by a Cox multivariate (MVA) proportional-hazards model and propensity score analyses with inverse probability treatment weighting (IPTW). RESULTS: We identified 6,301 patients; 51.2% had IRFs only and 48.8% had HRFs. Regarding treatment, 25.5%, 38.2%, and 36.3% of patients received no RT, PORT, and POCRT, respectively. Patients with IRFs who did not receive RT or CRT had inferior 8-year OS (81.1% vs. 87.8%; p < 0.001) that remained significant on IPTW MVA (hazard ratio (HR) = 1.69 (95% CI: 1.27-2.24; p < 0.001). Among patients with HRFs, 8-year OS was not significantly different between patients receiving PORT vs. POCRT (77.3% vs. 79.2%; p = 0.22) that remained insignificant on IPTW MVA (HR = 0.91(0.72-1.17); p = 0.48). CONCLUSION: A significant proportion of HPV-associated OP-SCC patients with IRFs or HRFs did not receive PORT, which was associated with inferior OS. We did not demonstrate with statistical power that POCRT vs. PORT was associated with superior OS in patients with HRFs, though prospective studies are warranted.

Predictors of prolonged treatment time intervals in oral cavity cancer.

OBJECTIVES: Delays in treatment time intervals have been associated with overall survival in oral cavity squamous cell carcinoma (OCSCC). The aim of this study was to identify bottlenecks leading to prolonged treatment intervals. MATERIAL AND METHODS: A retrospective analysis was conducted using a cohort of OCSCC patients who underwent surgery and adjuvant radiation therapy. The endpoints of interest were prolonged treatment intervals. Multivariable logistic regression was used to adjust for patient and tumour characteristics. RESULTS: Median diagnosis-to-treatment interval (DTI) and surgery to initiation of postoperative radiation therapy interval (S-PORT) were 39 days (IQR 30-54) and 64 days (IQR 54-66), respectively. Prolonged DTI was associated with older age, worse Charlson Comorbidity index scores and worse T stages. Patients with prolonged DTI had longer times to preoperative imaging reports (25 vs 9 days; P < 0.01). Time to preoperative pathology did not differ. Prolonged S-PORT was associated with longer times to pathology report (28 vs 18 days; P < 0.01), to maxillofacial consult (38 vs 15 days; P < 0.01) and to maxillofacial approval of radiation (50 vs 28 days; P < 0.01). In patients requiring medical oncology consults, those with prolonged S-PORT had longer waiting times until consultation (58 vs 38 days; P = 0.02). Multivariate analysis showed independent predictors of prolonged DTI: time to preoperative imaging; and prolonged S-PORT: time to pathology report, time to maxillofacial consult, and time to medical oncology consult. CONCLUSIONS: Strategies targeting these organizational bottlenecks may be effective for shortening treatment time intervals, hence representing potential opportunities for improving oncological outcomes in OCSCC patients.

Skeletal-Related Events After Surgery With or Without Radiotherapy for Bone Metastases to Weight-Bearing Bones.

Introduction In patients with metastatic disease involving weight-bearing bones, postoperative radiotherapy (PORT) is commonly administered following surgical stabilization of an impending or confirmed pathologic fracture to reduce the risk of a seeded local recurrence. The goal was to re-evaluate the beneficial effect of PORT in a modern cohort of patients and determine any potential clinical predictors of skeletal-related events (SREs) which were defined as a pathologic fracture or the necessity for radiation or surgery to the affected bone. Methods Consecutive patients undergoing surgical stabilization of metastatic disease to weight-bearing bones of the extremities between 2012 and 2019 were reviewed. Patient, disease, and treatment factors were abstracted. The cumulative incidence of SREs was determined using competing risks methodology; overall survival (OS) was estimated using the Kaplan-Meier method.  Results A total of 82 patients were identified, 74% of whom had undergone intramedullary nail fixation and 26% internal fixation or replacement. The femur was the most commonly involved bone (94%). A majority (78%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 1-2. Bone-strengthening agents were given to 38% and PORT to 54%. The median PORT dose was 30 Gy in 10 fractions and the median percent coverage of surgical hardware was 100% (range, 25-100). SREs occurred in 10 of 82 patients. There were no differences between no RT and RT groups for the two-year cumulative incidence of SREs (8.2% vs 11.5%, p=0.59) or two-year cumulative incidence of local failure (10.8% vs 4.6%, p=0.53). The only identified predictors of SREs were the use of bone-strengthening agents (hazard ratio [HR] 0.22, 95% confidence interval [CI] 0.05-1.06, p=0.06) and malnutrition (HR 3.69, 95% CI 0.91-14.93, p=0.07). For patients treated with PORT, a biologically effective dose or percent coverage of surgical hardware was not associated with SREs. Conclusion In this series, the addition of PORT following surgery for metastatic disease involving weight-bearing bones does not significantly affect the rate of SREs. The use of bone-strengthening agents appears protective, and malnourished patients appear particularly at high risk for future SRE.

Rural-urban differences in secular trends of locoregional treatment for ductal carcinoma in situ: A patterns of care analysis.

PRECIS: Omission of PORT following BCS remains high among rural patients despite evidence that PORT leads to a significant reduction in the risk of local recurrence. Further research is needed to examine the impact of rural residence on treatment choices and develop methods to ensure equitable care among all breast cancer patients. BACKGROUND: Despite national guidelines, debate exists among clinicians regarding the optimal approach to treatment for patients diagnosed with ductal carcinoma in situ (DCIS). While regional variation in practice patterns has been well documented, population-based information on rural-urban treatment differences is lacking. METHODS: Data from the SEER Patterns of Care studies were used to identify women diagnosed with histologically confirmed DCIS who underwent cancer-directed surgery in the years 1991, 1995, 2000, 2005, 2010, and 2015. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using weighted multivariable logistic regression to evaluate cancer-directed surgery and use of post-operative radiation therapy (PORT). RESULTS: Of the 3337 patients who met inclusion criteria, 27% underwent mastectomy, 26% underwent breast-conserving surgery (BCS) without PORT, and 47% underwent BCS with PORT. After adjustment for other covariates, there was no difference in the likelihood of receiving mastectomy between rural and urban patients (aOR = 0.65; 95% CI 0.37-1.14). However, rural residents were more likely than urban residents to have mastectomy during 1991/1995 (aOR = 1.78; 95% CI 1.09-2.91; pinteraction  = 0.022). Across all diagnosis years, patients residing in rural areas were less likely to receive PORT following BCS compared to urban patients (aOR = 0.35; 95% CI 0.18-0.67). CONCLUSIONS: Omission of PORT following BCS remains high among rural patients despite evidence that PORT leads to a significant reduction in the risk of local recurrence. Further research is needed to examine the impact of rural residence on treatment choices and develop methods to ensure equitable care among all breast cancer patients.

Timing of postoperative radiation therapy and survival in resected salivary gland cancers: Long-term results from a single institution.

OBJECTIVES: Timely administration of postoperative radiation therapy (PORT) impacts oncologic outcomes in resected squamous cell carcinomas of the head and neck. Salivary gland cancers (SGCs) are uncommon, and timing of PORT has not been extensively explored. We aimed to determine if the interval between surgery and PORT impacts outcomes in SGCs. MATERIALS AND METHODS: This is a retrospective study of patients with SGCs who underwent curative intent surgical resection followed by adjuvant PORT. Locoregional recurrence free survival (LRFS), disease free survival (DFS), and overall survival (OS) were estimated using the Kaplan Meier method. A multivariate analysis explored the association between demographics, tumor characteristics, and PORT timing with oncologic outcomes using a stepwise Cox proportional hazards model. RESULTS: 180 eligible patients were identified. The median time to PORT start was 61 (range 8-121) days. 169 (93.5%) of patients received neutron radiation. With a median follow up of 8.2 years in surviving patients, the 10-year OS and LRFS estimates were 61% and 53%. In a multivariate analysis, nodal involvement, histologic grade, and age at diagnosis were associated with OS, while nodal involvement, tumor size, and age at diagnosis were associated with LRFS and DFS. Time to PORT start or completion was not statistically associated with survival outcomes. CONCLUSION: SGC patients who underwent surgery in our tertiary institution received PORT within a median of 61 days after surgery. With long term follow up, PORT timing in this retrospective series was not associated with worse oncologic outcomes, and support timely administration of PORT.

Duration of radiation therapy is associated with worse survival in head and neck cancer.

INTRODUCTION: Delays in radiation are multifactorial, frequent, and associated with poor outcomes. This study investigates the effect of both primary and adjuvant radiation therapy duration and their interaction with other measures of treatment delay on survival in head and neck squamous cell carcinoma (HNSCC). METHODS: We built a retrospective cohort using the National Cancer Database, consisting of primary oral cavity, hypopharynx, larynx and oropharynx squamous cell carcinoma without distant metastasis and with at least six weeks of radiation. The primary exposure was the duration of radiation therapy (DRT), and the primary outcome was death. We estimated the association between DRT and 5-year overall survival (OS) using Kaplan-Meier curves and hazard ratios (HRs) with Cox proportional hazard regression. RESULTS: In both primary (definitive) and adjuvant (post-surgical) radiation settings, increased DRT results in decreased survival. In the primary radiation cohort, 5-year OS was 59.7% [59.1%-60.3%] among those with 47-53 days DRT, which decreased significantly with each subsequent week to completion (81+ days: 38.4% [36.2%-40.7%]). In the surgical cohort, survival decreased 16.5% when DRT extended beyond 75 days (40-46 days: 68.2% [67.3%-69.1%] vs. 75+ days: 53.3% [50.1%-56.7%]). Multivariate analyses showed increased hazard of death with increased DRT (primary radiation: 81+ days HR: 1.69 [1.58-1.81]); surgical: 75+ days HR: 1.61 [1.37-1.88]), with effects intensifying when restricting to those receiving full-dose radiation. CONCLUSION: A prolonged DRT was associated with worse OS in head and neck cancer. Radiation treatment delays of even a week lead to a significant survival disadvantage. DRT had a stronger association with survival than time to initiation of postoperative adjuvant radiotherapy.

Proton therapy for post-operative radiation therapy of non-small cell lung cancer.

Post-operative radiation therapy (PORT) is typically recommended for patients with locally advanced non-small cell lung cancer (NSCLC) with N2 mediastinal nodal involvement after surgical resection. The routine use of PORT, however, is controversial as older data demonstrated a detriment in overall survival in patients who received PORT. This detriment was thought to be due to older, more toxic radiation techniques. More recent data with modern radiation techniques demonstrates a local-regional and overall survival benefit with PORT in patients with N2 nodal involvement. Due to the competing risks of local-regional recurrence and cardiopulmonary toxicity in patients who are candidates for PORT, methods to widen the therapeutic window are needed. The physical characteristics of proton beam therapy allow for less radiation dose to the heart and lungs. Therefore, proton beam therapy has great potential in patients undergoing PORT. Initial dosimetric and clinical data have been published and are encouraging, but prospective data is needed to further understand the true benefit of proton therapy in patients undergoing PORT.

The expanding role of radiation therapy for thymic malignancies.

The role of radiation therapy (RT) in thymic malignancies has long been subject to considerable controversy. The main role for RT is in the setting of adjuvant therapy after surgical tumor resection, especially in advanced or incompletely resected cases. However, recent studies with larger patient numbers and cleaner study populations than previous studies have indicated a potentially clearer than previously assumed benefit after post-operative RT (PORT) even for completely resected patients with earlier stages of thymoma. In marginally resectable patients RT may be used in combination with neoadjuvant chemotherapy to shrink tumors and thereby potentially enable resection. In unresectable patients concurrent or sequential chemotherapy and RT can be employed as the definitive nonsurgical approach. The tendency of thymic tumors to recur in the pleural space highlights the necessity for more effective approaches to identify and treat high risk patients. Experiences in other pleural malignancies may pave the way to novel treatment modalities, for example pleural IMRT. The role of these techniques in thymic malignancies has yet to be determined and is not advisable at the current time outside of a clinical study. As the disease often takes an indolent course with excellent long-term local control (LC) and survival, late toxicities related to radiation of the mediastinum and adjacent organs at risk (OARs) have to be taken into consideration and may jeopardize the benefit patients experience from RT, especially in younger patients with a long-anticipated life expectancy. Radiation techniques, such as intensity modulated RT (IMRT) and proton beam therapy (PBT), have substantially reduced the exposure of OARs to ionizing radiation which is expected to translate into reduced long-term toxicities. Hence, the risk-benefit ratio of RT in early stage thymoma patients may be shifted favorably.

Proton Beam Therapy for Non-Small Cell Lung Cancer: Current Clinical Evidence and Future Directions.

Lung cancer is the leading cancer cause of death in the United States. Radiotherapy is an essential component of the definitive treatment of early-stage and locally-advanced lung cancer, and the palliative treatment of metastatic lung cancer. Proton beam therapy (PBT), through its characteristic Bragg peak, has the potential to decrease the toxicity of radiotherapy, and, subsequently improve the therapeutic ratio. Herein, we provide a primer on the physics of proton beam therapy for lung cancer, present the existing data in early-stage and locally-advanced non-small cell lung cancer (NSCLC), as well as in special situations such as re-irradiation and post-operative radiation therapy. We then present the technical challenges, such as anatomic changes and motion management, and future directions for PBT in lung cancer, including pencil beam scanning.