Safety and Efficacy of Stereotactic Body Radiation Therapy for Ultra-central Thoracic Tumors: A Single Center Retrospective Review.

PURPOSE: We sought to evaluate the toxicity and efficacy of stereotactic body radiation therapy (SBRT) for ultracentral thoracic tumors at our institution. METHODS AND MATERIALS: Patients with ultracentral lung tumors or nodes, defined as having the planning target volume (PTV) overlapping or abutting the central bronchial tree and/or esophagus, treated at our institution with SBRT between 2009 and 2019 were retrospectively reviewed. All SBRT plans were generated with the goal of creating homogenous dose distributions. The primary endpoint was incidence of SBRT-related grade ≥3 toxicity, defined using the Common Terminology Criteria for Adverse Events (V5.0). Secondary endpoints included local failure (LF), progression-free survival (PFS), and overall survival. Competing risk analysis was used to estimate incidence and identify predictors of severe toxicity and LF, while the Kaplan-Meier method was used to estimate PFS and OS. RESULTS: A total of 154 patients receiving 162 ultracentral courses of SBRT were included. The most common prescription was 50 Gy in 5 fractions (42%), with doses ranging from 30 to 55 Gy in 5 fractions (BED10 range, 48-115 Gy). The incidence of severe toxicity was 9.4% at 3 years. The most common severe toxicity was pneumonitis (n = 4). There was 1 possible treatment-related death from pneumonitis/pneumonia. Predictors of severe toxicity included increased PTV size, decreased PTV V95%, lung V5 Gy, and lung V20 Gy. The incidence of LF was 14% at 3 years. Predictors of LF included younger age and greater volume of overlap between the PTV and esophagus. The median PFS was 8.8 months, while the median overall survival was 44.0 months. CONCLUSIONS: In the largest case series of ultracentral thoracic SBRT to date, homogenously prescribed SBRT was associated with relatively low rates of severe toxicity and LF. Predictors of toxicity should be interpreted in the context of the heterogeneity in toxicities observed.

Solitary Intracranial Plasmacytoma of the Brain Treated With Primary Radiation Therapy.

We present a rare case of a solitary intracranial plasmacytoma of the brain parenchyma in a 49-year-old female who presented with neck pain/headache, paresthesias, and auditory hallucinations. A workup revealed a solitary left parietal lobe brain lesion and a biopsy demonstrated a plasma cell infiltrate consistent with an extramedullary plasmacytoma. A complete workup for multiple myeloma was negative. As opposed to surgical resection and adjuvant radiation therapy (RT), as described in prior case reports in the literature, this patient was managed with definitive local RT alone to 50 Gy in 25 fractions. Six months following primary RT completion, the patient's presenting symptoms completely resolved and follow-up imaging revealed regression of the primary tumor. To our knowledge, this is the first reported case of a solitary extramedullary plasmacytoma of the brain treated with localized definitive RT alone.

Survival in Metastatic Renal Cell Carcinoma Treated With Immunotherapy and Stereotactic Radiation Therapy or Immunotherapy Alone: A National Cancer Database Analysis.

Purpose: Immunotherapy (IO) has significantly improved outcomes in metastatic renal cell carcinoma (mRCC). Preclinical evidence suggests that responses to IO may be potentiated via immunomodulatory effects of stereotactic radiation therapy (SRT). We hypothesized that clinical outcomes from the National Cancer Database (NCDB) would demonstrate improved overall survival (OS) in patients with mRCC receiving IO + SRT versus IO alone. Methods and Materials: Patients with mRCC receiving first-line IO ± SRT were identified from the NCDB. Conventional radiation therapy was allowed in the IO alone cohort. The primary endpoint was OS stratified by the receipt of SRT (IO + SRT vs IO alone). Secondary endpoints included OS stratified by the presence of brain metastases (BM) and timing of SRT (before or after IO). Survival was estimated using Kaplan-Meier methodology and compared via the log-rank test. Results: Of 644 eligible patients, 63 (9.8%) received IO + SRT, and 581 (90.2%) received IO alone. Median follow-up time was 17.7 months (range, 2-24 months). Sites treated with SRT included the brain (71.4%), lung/chest (7.9%), bones (7.9%), spine (6.3%), and other (6.3%). OS was 74.4% versus 65.0% at 1 year and 71.0% versus 59.4% at 2 years for the IO + SRT and IO alone groups, respectively, although this difference did not reach statistical significance (log-rank P = .1077). In patients with BM, however, 1-year OS (73.0% vs 54.7%) and 2-year OS (70.8% vs 51.4%) was significantly higher in those receiving IO + SRT versus IO alone, respectively (pairwise P = .0261). Timing of SRT (before or after IO) did not influence OS (log-rank P = .3185). Conclusions: Patients with BM secondary to mRCC had prolonged OS with the addition of SRT to IO. Factors such as International mRCC Database Consortium risk stratification, oligometastatic tumor burden, SRT dose/fractionation, and utilization of doublet therapy should be considered in future analyses to better identify patients who may benefit from combined IO + SRT. Further prospective studies are warranted.

Overall survival in advanced hepatocellular carcinoma treated with concomitant systemic therapy and stereotactic body radiation therapy or systemic therapy alone.

Introduction: First-line systemic therapy (ST) options for advanced hepatocellular carcinoma (HCC) include tyrosine kinase inhibitors and immunotherapy (IO). Evolving data suggest prolonged overall survival (OS) when ST is combined with stereotactic body radiation therapy (SBRT), although evidence is significantly limited in HCC populations. We hypothesized that advanced HCC patients in the National Cancer Database (NCDB) would have improved OS when receiving ST+SBRT vs ST alone. Methods: Stage III/IV HCC patients diagnosed from 2010-2020 and treated with first-line ST±SBRT were identified from the NCDB. The primary endpoint was OS from date of diagnosis stratified by the receipt of SBRT (ST+SBRT vs ST alone). Survival was estimated using Kaplan-Meier methodology and compared via log-rank. Multivariate analysis (MVA) was performed by Cox regression. Results: Of 10,505 eligible patients with stage III disease, 115 (1.1%) received ST+SBRT and 10,390 (98.9%) received ST alone. Of 9,617 eligible patients with stage IV disease, 127 (1.3%) received ST+SBRT and 9,490 (98.7%) received ST alone. Median follow-up time was 6.8 months. Baseline characteristics were similar between cohorts. Patients with stage III disease receiving ST+SBRT had improved median OS (12.62 months vs 8.38 months) and higher rates of survival at 1-year (53.0% vs 38.7%) and 2-years (27.0% vs 20.7%) compared to those receiving ST alone (log-rank P=0.0054). Similarly, patients with stage IV disease receiving ST+SBRT had improved median OS (11.79 months vs 5.72 months) and higher rates of survival at 1-year (49.6% vs 26.2%) and 2-years (23.6% vs 12.0%) (log-rank P<0.0001). On MVA, receipt of SBRT predicted improved OS (HR=0.748, 95%CI 0.588-0.951; P=0.0178) and receipt of IO trended towards improved OS (HR=0.859, 95%CI 0.735-1.003; P=0.0538). Conclusion: In advanced HCC, patients receiving ST+SBRT had improved OS compared to those receiving ST alone. Prospective clinical trials are warranted to better identify HCC populations which may benefit from combined modality therapy.

Stereotactic Body Radiation Therapy for Mediastinal and Hilar Lymph Node Metastases.

PURPOSE: Stereotactic body radiation therapy (SBRT) to metastatic mediastinal and hilar lymphadenopathy (MHL) is challenging owing to the proximity of centrally located organs-at-risk. As limited data exist on the safety and efficacy of SBRT for MHL, a retrospective review of clinical outcomes was conducted from a large academic center. METHODS AND MATERIALS: Eligible patients received SBRT to MHL between 2014 to 2019 for the following indications: oligometastases, oligoprogression, or local control of a dominant area of progression. The primary endpoint was grade ≥3 toxicity (Common Terminology Criteria for Adverse Events, version 5.0). The cumulative incidence function evaluated local failure (LF) and starting or changing systemic therapy (SCST). Kaplan-Meier methodology estimated progression-free survival (PFS) and overall survival (OS). RESULTS: Fifty-two patients (84 metastases) were included. Median follow-up was 20 months. Primary cancer sites included kidney (53.8%), lung (13.4%), breast (7.7%), and other (25.1%). Indications for SBRT were oligoprogression (n = 35; 67.3%), oligometastases (n = 10; 19.2%), or local failure of a dominant area of progression (n = 7; 13.5%). The majority (n = 31; 59.6%) received SBRT to a single lymph node metastasis. Median SBRT dose was 35 Gy (range, 30-50 Gy) with a median biologically effective dose of 59.5 Gy (range, 48-100 Gy). All treatments were in 5 fractions. Seven grade ≥3 toxicities were experienced by 6 patients (11.5%) and were mostly transient (5/7; 71%). There was a single (1.9%) grade 5 toxicity (radiation pneumonitis). The cumulative incidence of LF was 9.0% at 2 years. The cumulative incidence of SCST was 33.2% and 57.1% at 1 and 2 years, respectively. Median PFS was 4.0 months (95% confidence interval, 2.8-7.3) and median OS was 31.7 months (95% confidence interval, 23.8-87.5). CONCLUSIONS: In one of the largest single institutional series of SBRT for MHL, moderate rates of grade ≥3 toxicity were observed, although the majority were transient. This treatment resulted in low LF rates and potentially delayed SCST for many patients.

Current Management and Progress in Radiotherapy for Small Cell Lung Cancer.

Radiotherapy (RT) and chemotherapy continue to be widely utilized in small cell lung cancer (SCLC) management. In most limited stage (LS)-SCLC cases, the standard initial therapy remains concurrent chemoradiotherapy (CRT), typically with an etoposide and platinum-based regimen. Hyperfractionated twice daily (BID) RT remains the standard of care, though conventional daily (QD) RT is now a viable alternative supported by randomized evidence. In LS-SCLC patients who experienced good response to CRT, prophylactic cranial irradiation (PCI) remains the standard of care. Brain imaging, ideally with MRI, should be performed prior to PCI to screen for clinically apparent brain metastases that may require a higher dose of cranial irradiation. Platinum doublet chemotherapy alone is the historic standard initial therapy in extensive stage (ES)-SCLC. Addition of immunotherapy such as atezolizumab and durvalumab to chemotherapy is now recommended after their benefits were demonstrated in recent trials. In patients with response to chemotherapy, consolidation thoracic RT and PCI could be considered, though with caveats. Emergence of hippocampal avoidance cranial irradiation and SRS in SCLC patients may supplant whole cranial irradiation as future standards of care. Incorporation of novel systemic therapies such as immunotherapies has changed the treatment paradigm and overall outlook of patients with SCLC. This narrative review summarizes the current state, ongoing trials, and future directions of radiotherapy in management of SCLC.

Overall and chemotherapy-free survival following stereotactic body radiation therapy for abdominopelvic oligometastases.

INTRODUCTION: Limited data establish the efficacy and safety of SBRT in the abdominopelvic (AP) space, where SBRT delivery is challenging due to the proximity of radiosensitive luminal gastrointestinal (GI) organs. The aim of this study was to assess clinical outcomes in patients with AP OM treated with SBRT. METHODS: Eligible patients were those with OM (defined as metastases in ≤3 total sites) in the AP space (excluding liver) treated with SBRT. Descriptive statistics and Kaplan-Meier estimates of (LC), progression-free survival (PFS), overall survival (OS) and chemotherapy-free survival (CFS) were performed. RESULTS: Fifty-one patients with 58 AP OM received SBRT between 2011 and 2015. Median follow-up was 21.9 months. All SBRT treatments were delivered in 5 fractions with a median dose of 35 Gy (25-40 Gy). Progression post-SBRT occurred in 38/51 patients (75%), with a median PFS of 4.9 months (95% CI: 2.5-7.5), and 2-year PFS of 29%. Rates of 2-and 4-year LC were 74% and 69%, respectively. Median OS was 42.6 months (95% CI: 31-55). Oligometastatic progression occurred in 21/38 patients, and of those, 48% (10/21) received further SBRT. Resulting 2- and 4-year CFS were 47% and 37%, respectively (median 15.1 months). Nineteen patients (37%) experienced a grade 1 or 2 acute toxicity. One grade 3 (acute) toxicity was observed. No grade 4 or 5 toxicities were detected. CONCLUSIONS: SBRT to AP OM was associated with sustained LC, excellent OS and minimal toxicity. The use of SBRT allowed for prolonged CFS and the salvage of limited-burden distant failures.

Treatment outcomes of locally advanced oropharyngeal cancer: a comparison between combined modality radio-chemotherapy and two variants of single modality altered fractionation radiotherapy.

PURPOSE: To compare outcomes in patients with locally advanced oropharyngeal cancer treated with radio-chemotherapy (RT-CT), accelerated fractionation radiotherapy (AccRT), or hypofractionated radiotherapy (HypoRT). METHODS AND MATERIALS: Subjects were 321 consecutive patients with newly diagnosed oropharyngeal cancer, Stage III or IVA/B, treated between January 2001 and December 2005 at the BC Cancer Agency with RT-CT (n = 157), AccRT (n = 57), or HypoRT (n = 107). Outcomes examined were disease-specific survival (DSS), locoregional control (LRC), overall survival (OS), rate of G-tube use, and rate of hospitalization for acute complications. RESULTS: Median follow-up was 3.4 years. Three-year Kaplan-Meier DSS with RT-CT, AccRT, and HypoRT were 80%, 81%, and 74%, respectively (p = 0.219). Cox regression analysis identified treatment modality as a significant factor affecting DSS (p = 0.038). Compared with RT-CT, the hazard ratio (HR) for DSS was 1.0 with AccRT and 2.0 with HypoRT (p = 0.021). Kaplan-Meier pairwise comparisons found no significant difference in LRC and OS between RT-CT and AccRT. HypoRT was associated with significantly lower LRC (p = 0.005) and OS (p = 0.008) compared with RT-CT. There were significant differences in the rates of G-tube use (p < 0.001) and of hospitalization (p = 0.036) among the three treatment groups, with the most frequent rates observed in the RT-CT group. CONCLUSIONS: In patients with locally advanced oropharyngeal cancer, AccRT conferred DSS, LRC, and OS comparable to that of RT-CT. Patients treated with RT-CT experienced higher rates of treatment-related acute toxicities. HypoRT was associated with the least favorable outcomes.