Local Control Survival Research Articles

Postoperative Stereotactic Body Radiotherapy for Spinal Metastasis and Predictors of Local Control.

Spine surgery is indicated for select patients with mechanical instability, pain, and/or malignant epidural spinal cord compression, with or without neurological compromise. Stereotactic body radiotherapy (SBRT) is an option for durable local control (LC) for metastatic spine disease. To determine factors associated with LC and progression-free survival (PFS) for patients receiving postoperative stereotactic spine radiosurgery. We analyzed consecutive patients from 2013 to 2019 treated with surgical intervention followed by SBRT. Surgical interventions included laminectomy and vertebrectomy. SBRT included patients treated with 1 to 5 fractions of radiosurgery. We analyzed LC, PFS, overall survival (OS), and toxicity. Univariate and multivariate analyses were performed. A total of 63 patients were treated with a median follow-up of 12.5 mo. Approximately 75% of patients underwent vertebrectomy and 25% underwent laminectomy. One-year cumulative incidence of local failure was 19%. LC was significantly improved for patients receiving radiosurgery ≤40 d from surgery compared to that for patients receiving radiosurgery ≥40 d from surgery, 94%vs 75%, respectively, at 1 yr (P=.03). Patients who received preoperative embolization had improved LC with 1-yr LC of 88%vs 76% for those who did not receive preoperative embolization (P=.037). Significant predictors for LC on multivariate analysis were time from surgery to radiosurgery, higher radiotherapy dose, and preoperative embolization. The 1-yr PFS and OS was 56% and 60%, respectively. Postoperative radiosurgery has excellent and durable LC for spine metastasis. An important consideration when planning postoperative radiosurgery is minimizing delay from surgery to radiosurgery. Preoperative embolization and higher radiotherapy dose were associated with improved LC warranting further study.

Spinal Cord Tolerance After High Dose, De Novo, Single Fraction Spine Stereotactic Radiosurgery

Spine stereotactic radiosurgery (SSRS) offers high rates of local control (LC) in a critical anatomic area by delivering precise, ablative doses of radiation. However, there remains uncertainty regarding the single fraction dose tolerance of the spinal cord (SC) after SSRS. This is of considerable importance as limiting dose to the SC to prevent radiation myelopathy (RM) may lead to underdosing of tumor and ultimately, treatment failure. Here, we report on our experience with relaxed SC dose constraints during SSRS for spinal metastases. We reviewed patients who underwent single fraction, de novo SSRS from 2012 - 2017 at our institution and received >12 Gy Dmax to the SC, which was defined using MRI-CT fusion without PRV expansion. CT myelogram was only used if instrumentation was present. The standard SC constraint was D0.01cc ≤12 Gy, but could be exceeded on protocol for high-risk, inoperable patients. Patients with radioresistant and radiosensitive histologies were treated with 16 Gy to the CTV and a SIB to the GTV of 24 Gy and 18 Gy, respectively, without PTV margin. Patients were rigidly immobilized and aligned with stereoscopic imaging, cone-beam CT, and kV/mV imaging. LC and overall survival (OS) were analyzed with the Kaplan-Meier method. Non-informative beta priors of RM from published studies were used to compute posterior probabilities for the true rate of RM. A total of 132 patients and 146 unique SSRS treatments were analyzed. The median age was 63 years, 70% were male, and 90% had ECOG PS of 0-1. Most patients had renal cell carcinoma (42%), were treated at the thoracic level (86%), and had epidural disease (55%). A minority (16%) had high grade (Bilsky 1c or 2) epidural disease. The median SC Dmax was 12.6 Gy (range, 12.1–17.1 Gy). The SC Dmax was >12 and <13 Gy for 109 (75%) treatments, ≥13 and <14 Gy for 26 (18%) treatments, and ≥14 Gy for 11 (7%) treatments. The median OS was 2.2 years and the 1- and 2-year LC rates were 94% and 92%, respectively. With a median follow up time of 3.5 years, there were zero (0) RM events observed in the cohort. Assuming a conservative prior 4.3% risk of RM, we calculated the true rate of RM for SC Dmax of ≤14 Gy to be <1% with 98% confidence at 24 months. Similarly, we calculated the true rate of RM for SC D0.1cc ≤10 Gy and D1cc ≤8 Gy to be <1% at 24 months with high confidence (Table 1). In one of the largest series of patients treated with single fraction, de novo SSRS to date, there were no cases of RM observed with a median follow up of 3.5 years. These data provide rationale for the safe relaxation of MRI-defined spinal cord dose up to D0.01cc ≤12 Gy and with careful selection, Dmax ≤14 Gy, which correspond to a <1% risk of RM and may allow for durable local control even in those patients with high-risk disease.Abstract 3740; TableSpinal Cord Dose ThresholdPrior Probability of RMConfidence that True Rate of RM < rr = 0.1%r = 0.5%r = 1%r = 2%r = 3%Dmax ≤ 14 Gy4.3%90.5%96.1%98.0%99.3%99.7%D0.1cc ≤ 10 Gy0.53%97.8%98.6%99.0%99.3%99.5%D1cc ≤ 8 Gy0.53%98.1%99.0%99.3%99.6%99.7% Open table in a new tab

Simultaneous Reduction of Volume and Dose in Clinical Target Volume for Nasopharyngeal Cancer Patients

To compare the treatment outcome and severe late adverse effects (AEs) between conventional volume and dose (CVD) and simultaneously reduced volume and dose (SRVD) of clinical target volume treatments in patients with nasopharyngeal carcinoma. This retrospective cohort study enrolled patients with nonmetastatic stage II to IV nasopharyngeal cancer from a single institute. Survival endpoints and severe (≥grade 3) late AEs and comorbidity were compared between groups. The correlation of severe late AEs, comorbidity, and overall survival (OS) were evaluated using Kaplan-Meier and Cox regression methods. From January 2012 to June 2017, this study enrolled 178 patients, 64 in the CVD group and 114 in the SRVD group. The 2 groups did not differ significantly in patient characteristics except for mean follow-up time (37.6 vs 48.8 months; P = .01). The SRVD group did not significantly differ from the CVD group in local control survival (82.0% vs 78.4%; P = .85), regional control survival (89.9% vs 86.0%; P = .62), or disease-free survival (76.4% vs 66.9%; P = .67). The SRVD group had significantly better OS (93.9% vs 67.0%; P < .001) and salvage survival (79.3% vs 20.7%; P < .01) and a significantly lower ratio of severe lung infection (1 of 113 vs 5 of 59; P = .02). The SRVD group had a significantly lower risk of mortality (hazard ratio [HR], 0.3; P = .03). The factors associated with a significantly higher risk of mortality were N3 (regional lymph node stage status of N3) (HR, 3.0; P = .02); comorbidities of diabetes, coronary artery disease, or chronic kidney disease (grades 2-3) (HR, 3.8; P = .009), and severe lung infection (HR, 6.3; P = .007). Simultaneously reduced volume and dose of clinical target volumes did not impair locoregional control or disease-free survival. The benefits of SRVD treatment may include significant reduction in severe late AEs, particularly lung infection, dysphagia, and xerostomia. However, additional studies with longer patient follow-up are required to confirm these benefits.

Dose-response relationship of stereotactic body radiotherapy for ultracentral tumor and comparison of efficacy with central tumor: a meta-analysis.

BackgroundUltracentral (UC) tumors, a subset of central lung tumors defined as those that abut the proximal bronchial tree (PBT), have been contraindicated for stereotactic body radiotherapy (SBRT). The present meta-analysis evaluated the efficacy of SBRT for UC and central tumors, and dose-response for local control (LC) of UC tumors.MethodsDatabases including MEDLINE and EMBASE were searched up to March, 2020, to identify studies regarding SBRT for UC and/or central tumors. The primary endpoints were LC and overall survival (OS), while secondary endpoints were grade ≥3 and 5 complications.ResultsFourteen studies including 892 patients were included. In the UC and central tumor groups, the 1-year OS rates were 82.2% and 85.4% (P=0.556), respectively, and the 2-year OS rates were 66.4% and 71.9% (P=0.522), respectively. The 1- and 2-year LC rates in the UC and central tumor groups were 93.9% and 97.8% (P=0.023) and 90.4% and 93.7% (P=0.459), respectively. The pooled grade ≥3 complication rates in the UC and central tumor groups were 9.0% and 4.4% (P=0.06), while the corresponding grade 5 complication rates were 5.7% and 2.1% (P=0.087). The dose-response for LC was shown in the meta-regression (P<0.0001), and 1-year LC rates were significantly different (94.4% vs. 59.3%, P<0.001) with very low heterogeneities in both subgroups, with threshold of 85 Gy10. Of the 28 fatalities, 12 (42.8%) were caused by hemorrhage or bronchial stenosis, and another 12 (42.8%) by pneumonia or respiratory failure.ConclusionsThe oncologic outcomes of patients with UC and central tumors were comparable post-SBRT. A dose of at least ≥85 Gy10 is recommended for SBRT of UC tumors. Causes of complications should be further studied as UC tumors are more prone to serious toxicities.

Multi-institutional analysis of stereotactic body radiotherapy for sarcoma pulmonary metastases: High rates of local control with favorable toxicity.

Oligometastatic sarcoma pulmonary metastases (PM's) are traditionally treated with resection and/or chemotherapy. We hypothesize that stereotactic body radiotherapy (SBRT) is an effective, safe alternative to surgery that can achieve excellent local control (LC) with a favorable toxicity profile. Patients treated with SBRT for sarcoma PM's from 2011 to 2016 at Massachusetts General Hospital and the University of Pennsylvania were included. Median dose was 50 Gy. Patients underwent computed tomography (CT) or positron emission tomography/CT Q3 months post-SBRT. 44 patients with 56 separate PM's were treated with SBRT. Median age was 59 (range 19-82). 82% received prior chemotherapy, 66% had prior pulmonary resections (range, 1-5 resections), and 32% received prior thoracic radiotherapy. Median lesion size was 2.0 cm (range, 0.5-8.1 cm). Median follow-up was 16 months and 25 months for patients alive at last follow-up. Overall survival at 12 and 24 months was 74% (95% confidence interval [CI], 67%-81%) and 46% (95% CI, 38%-55%). LC at 12 and 24 months was 96% (95% CI, 93%-98%) and 90% (95% CI, 84%-96%). LC and overall survival did not differ based on age, gender, histology, fractionation, lesion location, or size (P > .05). Three developed Common Terminology Criteria for Adverse Events version 4 grade-2 chest-wall toxicities; one had grade-2 pneumonitis. In the first multi-institutional series on SBRT for sarcoma PM's, SBRT has excellent LC and is well-tolerated. SBRT should be considered as an alternative/complement to resection.

Biologic subtypes as a predictor of local control in patients with brain metastases from breast cancer after stereotactic radiosurgery

Biological subtypes have been strongly correlated with loco-regional recurrence after definitive treatment for localized breast cancer. Brain metastases (BM) occur in 15% of patient diagnosed with breast cancer (BC). Therefore, we sought to determine whether biologic subtype is predictive of local control (LC) in BC patients with BM treated with stereotactic radiosurgery (SRS). This is a single-center retrospective study conducted with Institutional Review Board approval for the period January 1, 2004–December 31, 2018. Eligibility criteria included (1) histopathologic proven BC with documented biologic subtype, (2) presence of BM treated with SRS (single fraction), (3) follow-up MRIs, and (4) clinical follow-up. Patients were subdivided into three biologic subtypes: ER+/HER2- (“luminal”), HER2+, and ER-/PR-/HER2 (TN). All patients were treated with LINAC-based SRS with dose according to published guidelines. Cox proportional hazard model and Kaplan-Meier were used for statistical analysis of LC and overall survival (OS). With a median follow-up of 11.1 months, 17 BC BM in 50 consecutive patients were included in this study. The median disease-specific GPA was 2.0, and all patients received systemic chemotherapy and/or hormonal therapy. The 12-month LC rates for the entire cohort were 85%, 87%, and 49% for luminal, HER2+, and TN, respectively, with a significantly shorter time to local failure for the TN subtype (p = 0.014). The 12-month OS rates were 83%, 88%, and 80% for luminal, HER2+, and TN, respectively, with a trend toward shorter OS in the TN group. This study shows that in BC patients with BM treated with SRS, biologic subtype affects LC. Consideration of radiation treatment intensification or altered fractionation to improve LC may be indicated for the TN subtype. Further multicenter studies are necessary to corroborate our results.

Stereotactic Body Radiotherapy Combined with Transcatheter Arterial Chemoembolization versus Stereotactic Body Radiotherapy Alone as the First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Meta-Analysis and Systematic Review

Background: The superiority of stereotactic body radiotherapy (SBRT) combined with transcatheter arterial chemoembolization (TACE) compared to SBRT alone as the first-line therapy for unresectable hepatocellular carcinoma (HCC) remains unclear. We conducted this meta-analysis to compare the efficiency and safety of SBRT combined with TACE (ST group) and SBRT alone (SA group). Methods: We searched PubMed, Ovid Medline, Web of Science, Scopus, The Cochrane Library, ScienceDirect, EMBASE, Google Scholar, and CNKI (China National Knowledge Infrastructure) for related studies. We analyzed overall survival (OS), local control survival (LCS), progression-free survival (PFS), the response rate and adverse effects (AEs) between the 2 groups. Results: Ten articles were included, with a total of 980 patients. The results showed that the ST (SBRT + TACE) group had a longer OS (95% CIs 0.60–0.85, p = 0.0002), a higher 5-year OS rate (95% CI 1.01–2.04, p = 0.04), a higher rate of complete response (95% CI 1.08–1.90, p = 0.01), and a higher disease control rate (95% CI 1.02–1.16, p = 0.02) than the SA (SBRT alone) group. No significant difference was found in LCS, PFS and total AEs of all grades and grades 3–5 AEs between the 2 groups. In the subgroup analysis, the patients with HCC + PVTT or treated with SBRT followed by TACE in the ST group had the same OS as those in the SA group, and the patients in the ST group had a higher incidence rate of leukopenia and fever than those in the SA group. Conclusion: SBRT + TACE appears to be more effective than SBRT alone in treating unresectable HCC. However, its higher incidence rate of leukopenia and fever need to be monitored.

Prognostic factors of local control and disease free survival in centrally located non-small cell lung cancer treated with stereotactic body radiation therapy

Background: Stereotactic body radiation therapy (SBRT) results in high local control (LC) rates in patients with non-small cell lung cancer (NSCLC). For central lung tumors, risk-adapted fractionation schedules are used and underdosage to the Planned Target Volume (PTV) is often accepted to respect the dose constraints of the organs at risk in order to avoid high rates of toxicity. The purpose of this study was to analyze the effect of PTV underdosage and other possible prognostic factors on local- and disease control after SBRT in patients with central lung tumors.Material and Methods: Patients with centrally located NSCLC treated with SBRT were included. The doses were converted into biologically equivalent dose using α/β-value of 10 Gy (BED10). Underdosage to the PTV was defined as the (percentage of) PTV receiving less than 100 Gy BED10; (%)PTV < 100 BED10. Potential prognostic factors for LC and Disease Free Survival (DFS) were evaluated using Cox regression analysis.Results: Two hundred and twenty patients received ≤12 fractions of SBRT. LC-rates were 88% at 2 years and 81% at 3 years. Twenty-seven patients developed a local recurrence. Both the PTV < 100 BED10 and %PTV < 100 BED10 were not prognostic for LC. Tumor size and forced expiratory volume in 1 second (FEV1) were independently prognostic for LC. Disease progression was reported in 75 patients with DFS-rates of 66% at 2 years and 56% at 3 years. Disease recurrence was independent significantly associated with larger tumor diameter, lower lobe tumor location and decreased FEV1. Grade 4–5 toxicity was reported in 10 patients (8 with ultra-central tumors) and was fatal in at least 3 patients.Conclusion: Decrease in tumor coverage was not correlated with the local recurrence probability. The LC and DFS were promising after SBRT of centrally located NSCLC with tumor size, FEV1 and tumor location (for DFS only) as prognostic factors.

Efficacy of non-surgical larynx-preservation comprehensive treatment in advanced laryngeal carcinoma.

Efficacy of non-surgical larynx-preservation comprehensive treatment in advanced laryngeal carcinoma.

Tumor volume and sphericity as predictors of local control after stereotactic radiosurgery for limited number (1-4) brain metastases from nonsmall cell lung cancer.

This study aims to evaluate the usage of brain metastases (BM) tumor volume and sphericity as prognostic factors in local control (LC) after stereotactic radiosurgery (SRS) for limited number (1-4) BM from nonsmall cell lung cancer (NSCLC). We retrospectively reviewed 80 patients, with 141BM, who were treated with SRS from 2012 to 2017. Local failure was defined as an increase in lesion size after SRS. LC and overall survival (OS) were estimated using Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis. The median clinical and radiographic follow-up was 11.2 and 9.0 months, respectively. The median BM tumor volume was 0.31 cm3 (0.01-21.64 cm3 ) and the median tumor sphericity was 0.76 (0.39-0.95). The median LC of the entire cohort was 28.8 months. LC rate at last follow-up was achieved in 84.4% of patients (35.5% CR, 35.5% PR, and 13.5% SD). LC was 83.8% at 1 year and 56.3% at 2 years. On multivariate analysis, only sphericity (P<.001) and volume (P=.004) were found to be a strong predictor for LC. The median OS of the entire cohort was 24.1 months. On multivariate analysis, only GPA score was found to be a predictor for OS. BM tumor sphericity and volume were found to be strong predictors for LC. Tumor sphericity and volume should be taken into consideration when treating patients with BM and when designing future prospective studies and developing prognostic indices.

Residual Site Radiotherapy After Immunochemotherapy in Primary Mediastinal B-Cell Lymphoma: A Monoinstitutional Retrospective Study.

To evaluate the efficacy of residual site radiation therapy (RSRT) on local control (LC), progression-free (PFS) and overall (OS) survival in patients with primary mediastinal lymphoma (PMBCL), following rituximab and chemotherapy treatment (ICHT). The study included 34 patients with PMBCL treated between 2006 and 2014 with ICHT with/without autologous stem cell transplantation and RSRT. Between the end of ICHT/stem cell transplantation and RSRT, patients were evaluated with 18F-fluorodeoxyglucose positron-emission tomography. The gross tumor volume included morphological mediastinal residual disease after ICHT/SCT. The percentage of LC, PFS and OS were assessed. All patients received RSRT with a median dose of 30 Gy. Median follow-up was 82 months. One patient out of 34 (3%) showed progressive disease 9 months from diagnosis. The 10-year PFS and OS were 97% and 97% respectively. RSRT in patients with PMBCL treated with ICHT did not impact unfavorably on LC and patient survival.

Influence of dose-averaged linear energy transfer on tumour control after carbon-ion radiation therapy for pancreatic cancer

Background and purposeHigh linear energy transfer (LET) radiation carbon-ion radiotherapy (C-ion RT) is one of the most promising modalities for treating unresectable primary pancreatic cancers. However, how LET contributes to a therapeutic effect is not clear. To assess whether there is an enhanced effect of high LET radiation on tumour control, we aimed to determine the impact of dose-averaged LET on local control (LC) of primary pancreatic tumours. Materials and methodsA retrospective analysis of 18 patients with primary pancreatic carcinomas treated with definitive C-ion RT with concurrent chemotherapy in 2013 was conducted. The dose of irradiation was 55.2 Gy (RBE). The relationship between dose-averaged LET and LC of primary tumours was evaluated. ResultsAll patients had histologically confirmed adenocarcinoma. The median follow-up duration was 22 months. The actuarial LC and overall survival (OS) at 18 months were 62.5% and 70.1%, respectively. There were no cases of grade ≥3 late toxicities observed. Local recurrences developed in four patients (22%), all of which were infield central recurrences. Although there were no significant differences in gross tumour volume (GTV) dose coverage, patients with higher minimum dose-averaged LET (LETmin) values within the GTV had better LC (dose-averaged LETmin ≥44 keV/microm; 18-months LC 100.0% vs 34.3%; p = 0.0366). ConclusionDose-averaged LETmin within the GTV was significantly associated with LC of primary pancreatic cancers. Our data suggest that outcomes for patients with unresectable primary pancreatic cancers receiving C-ion RT can be improved by modulating the dose-averaged LET within the GTV.

Reduced‐volume tumor‐bed boost is not associated with inferior local control and survival outcomes in high‐risk medulloblastoma

Radiotherapy boost to the entire posterior fossa (PF) is standard of care for high-risk (H-R) medulloblastoma patients; the utility of tumor bed (TB)-only boost is unclear. The purpose of this study was to examine the impact of PF versus TB boost volume on tumor control and survival in the H-R medulloblastoma population. Single-institution records for patients with H-R medulloblastoma were reviewed. The median craniospinal irradiation dose was 36Gy (range, 23.4-45Gy), and boost doses to either PF or TB were 54 to 55.8Gy. PF (local) failures were scored as in-field, marginal (between 80% and 95% isodose lines), or distant. Kaplan-Meier methods and Cox proportional hazards were used to assess the impact of radiation boost technique on local control (LC) and survival endpoints. Thirty-two patients with H-R medulloblastoma were treated between 1990 and 2015, with a median follow-up length of 5.12 years. Twenty-two patients received PF boost, and 10 received TB boost. Patient and disease characteristic were comparable between groups. A total of 11 PF failures occurred, including 3 isolated LFs (2 in the PF and 1 in the TB group). Most PF failures were in-field: three of four in the TB group and six of seven in the PF group; the remainder were marginal failures. TB boost was not associated with inferior LC (hazard ratio [HR] 0.86, log-rank P=0.81) or overall survival (HR 1.40, P=0.56) compared with PF boost. Reduced-volume radiotherapy boost to the TB does not appear to compromise LC or survival in patients with H-R medulloblastoma; it may reduce the risk of ototoxicity.

Confirmation of thermal dose as a predictor of local control in cervical carcinoma patients treated with state-of-the-art radiation therapy and hyperthermia

BackgroundAddition of deep hyperthermia results in improved local control (LC) and overall survival (OS) compared to radiotherapy alone in patients with cervical carcinoma. Previously, we showed that the thermal dose of hyperthermia significantly correlates with LC and disease specific survival (DSS). Over the last decade, new radiation techniques were introduced resulting in improved LC. AimTo validate the effect of thermal dose in a more recent cohort of patients treated with modern radiotherapy techniques, including image guided brachytherapy (IGBT). MethodsWe analyzed primary cervical carcinoma patients treated with a combination of radiotherapy and deep hyperthermia between 2005 and 2016 at our institute. Data on patient, tumor and treatment were collected including the thermal dose parameters TRISE and CEM43T90. Follow-up data on LC, disease free survival, DSS, OS as well as late toxicity data were collected. Data were analyzed using the Cox proportional hazard and Kaplan–Meier analyses. Results227 patients were included. In multivariate analysis, histology, FIGO stage, lymphadenopathy, TRISE, CEM43T90 and IGBT had a significant effect on LC. In the patients treated with IGBT, the thermal dose parameter TRISE remained to have a significant effect on LC in univariate analysis. ConclusionsThe positive association between thermal dose and clinical outcome is replicated in an independent, recent cohort of cervical carcinoma patients. Importantly, in patients receiving IGBT, the effect of thermal dose on clinical outcome is still observed.

A Phase 1/2 Study of Carbon Ion Radiation Therapy With Concurrent Chemotherapy for Locally Advanced Uterine Cervical Squamous Cell Carcinoma (Protocol 1302)

This study evaluated the safety and efficacy of carbon-ion radiation therapy (C-ion RT) with concurrent chemotherapy for locally advanced uterine cervical squamous cell carcinoma in a phase 1/2 clinical trial. Twenty-two patients were treated with C-ion RT with concurrent weekly cisplatin at a dose of 40mg/m2. The phase 1 component evaluated the safety of 72.0Gy (relative biological effectiveness) of C-ion RT with concurrent chemotherapy. In the phase 2 component, the safety and efficacy of C-ion RT with concurrent chemotherapy were assessed using the dose determined in phase1. The median follow-up period was 32months, and the median tumor size was 71mm (range, 51-150mm). No patient had dose-limiting toxicities in the phase 1 component; the recommended dose was determined to be 72.0Gy (relative biological effectiveness) with 40mg/m2 of cisplatin. In the phase 2 component, 2 patients developed grade 3 gastrointestinal tract toxicities. In patients treated with the recommended dose, the 2-year local control (LC), LC including salvage therapy, and overall survival rates were 67%, 81%, and 82%, respectively. The 2-year LC and overall survival rates for patients with tumor sizes ≤7.1cm were 92% and 100%, respectively; for those with tumor sizes >7.1cm they were 33% and 60%, respectively. C-ion RT with concurrent weekly cisplatin was tolerated by patients with locally advanced uterine cervical squamous cell carcinoma. Outcomes were good in patients with tumor sizes ≤7.1cm but not in those with larger tumors. The results of the present study should be validated with larger multi-institutional prospective studies. Further study is needed, and perhaps incorporating carbon ion external beam radiation with brachytherapy will further reduce the risk of central recurrence.

Tumor Control and Toxicity after SBRT for Ultracentral, Central, and Paramediastinal Lung Tumors

PurposeIncreased rates of toxicity have been described after stereotactic body radiation therapy (SBRT) for central lung tumors within 2 cm of the proximal bronchial tree (PBT). Recent studies have defined a new class of ultracentral tumors. We report our experience treating ultracentral, central, and paramediastinal tumors with SBRT and compare toxicity, disease control, and survival rates. Methods and materialsWe reviewed the records of patients with central lung tumors treated with SBRT between September 2009 and July 2017. Tumors were classified as central if within 2 cm of the PBT, ultracentral if the planning target volume touched the PBT or esophagus, and paramediastinal if touching mediastinal pleura. Actuarial rates of grades 2+ and 3+ toxicity, local control (LC), and overall survival were assessed using the Kaplan-Meier method and compared using a log-rank test. Toxicity was scored with the Common Terminology Criteria for Adverse Events, version 4.03. ResultsWe identified 68 patients with 69 central lung tumors, including 14 ultracentral, 15 paramediastinal, and 39 central tumors. Fifty-three patients were treated for early stage lung cancer and 15 for lung metastases. The prescribed dose ranged from 40 Gy to 60 Gy over 3 to 8 fractions. Most patients were treated using 5 fractions (83%), followed by 8 fractions (10%). Median follow-up was 19.7 months (range, 3.3-78.3 months). The 2-year estimates of LC (89%, 85%, and 93%, respectively; P = .72) and overall survival (76%, 73%, and 72%, respectively; P = .75) for ultracentral, central, and paramediastinal tumors were similar. Ultracentral tumors had an increased risk of grade 2+ toxicity (57.6% vs 14.2% vs 7.1%; P = .007) at 2 years. One patient with an ultracentral tumor developed grade 5 respiratory failure. ConclusionsThe oncologic outcomes after SBRT for ultracentral, central, and paramediastinal lung tumors were similar, with LC exceeding 85% at 2 years using predominantly 5-fraction schedules. Ultracentral lung tumors were associated with an increased risk of toxicity in our patient cohort. Additional studies are needed to minimize toxicity for ultracentral tumors.

Stereotactic Body Radiation Therapy in Oligometastatic Ovarian Cancer: A Promising Therapeutic Approach.

Stereotactic body radiation therapy (SBRT) has been successfully used to treat oligometastases of several primary tumors, but few experiences have been described in patients with gynecological oligometastatic cancer, particularly in ovarian neoplasm. The aim of this study was to evaluate the role of this new radiotherapy modality in a series of oligometastatic ovarian cancer patients. Clinical records of patients affected by oligometastatic ovarian carcinoma treated with SBRT were reviewed. Twenty-six patients with 44 metastatic lesions (lymph nodes, 63.6%; liver, 31.8%; and lung, 4.5%) treated with SBRT between January 2011 and May 2017 were analyzed. After a median follow-up period of 28.5 months (range, 6-86 months), 17 patients (65.4%) were still alive at time of analysis: 6 are without evidence of disease, 11 experienced a disease progression. Eight patients died of disease, 1 died because of an heart attack while being disease free. The median local control (LC) was not reached. One-, 2-, and 5-year LCs were 92.9%. Median progression-free survival was 19 months, with 1-year progression-free survival of 69.3% and 38% at 2 years, 19% at 5 years. Median overall survival was 64.5 months, with all patients alive after 1 year, 92.7% at 2 years, and 61.7% at 5 years. Five (11.3%) cases experienced G2 toxicity; most common adverse effect was nausea and vomiting (3 cases [6.8%]) followed by abdominal pain (2 cases [4.5%]). None of the patients had grade 3 or grade 4 acute or late toxicity. In conclusion, SBRT is a feasible and safe approach for selected cases of oligometastatic ovarian cancer, with satisfactory results in terms of LC and disease free survival.

Comparison of Single- and Five-fraction Regimens of Stereotactic Body Radiation Therapy for Peripheral Early-stage Non–small-cell Lung Cancer: A Two-institution Propensity-matched Analysis

PurposeTo evaluate differences in local control (LC), disease-specific (DC), and overall survival (OS) of patients with early-stage non–small-cell lung cancer (NSCLC) treated with single- (SF) versus 5-fraction (FF) stereotactic body radiation therapy (SBRT) at 2 institutions. Patients and MethodsPeripheral early-stage NSCLC cases treated with a median dose of 30 Gy in SF or a median dose of 50 Gy in FF were included per institutional practice. Kaplan-Meier and Cox models were used to assess survival. A matched-pair analysis was performed to account for imbalances. Toxicities including Common Terminology Criteria for Adverse Events (CTCAE) grade 3 pneumonitis, chest wall pain requiring long-acting narcotics, and hospitalization for respiratory events 6 months posttreatment were recorded. ResultsA total of 163 lesions were treated between 2007 and 2015; 65 received SF SBRT and 98 received FF SBRT. Most tumors were T1 (n = 92) and T2 (n = 34) lesions and had adenocarcinoma (n = 77) and squamous cell carcinoma (n = 46) histologies, respectively. In the matched cohort, there were no differences in OS, LC, DC, or progression-free survival between the groups. LC and OS at 1 year in the matched cohort was 95% and 88%, and 87% and 84% in the SF and FF cohorts, respectively. There was 1 grade 3 pneumonitis in the FF group, and 9 total hospitalizations post-SBRT, 3 (5%) in the SF group and 6 (6%) in the FF group. ConclusionsNo statistically significant differences were seen in LC or DC following SF or FF SBRT in this matched cohort of peripheral lesions. No grade 4 or higher toxicities were reported.

Stereotactic Body Radiation Therapy for Biopsy-Proven Primary Non-Small-Cell Lung Cancer: Experience of Patients With Inoperable Cancer at a Single Brazilian Institution.

PurposeStereotactic body radiation therapy (SBRT) has emerged as a treatment option for patients with non–small-cell lung cancer (NSCLC). We report the clinical outcomes and toxicity for patients with inoperable primary NSCLC treated with SBRT.MethodsBetween 2007 and 2015, 102 consecutive lung lesions were treated with SBRT at our center, of which 59 primary NSCLC lesions (from 54 patients with inoperable disease) were retrospectively reviewed (43 lesions were excluded because of metastases or because there was no biopsy specimen). We report infield local control (LC) per SBRT target, regional or distant failure-free survival, and overall survival (OS) per patient, using Kaplan-Meier estimates. Serious toxicity was retrospectively scored using Common Terminology Criteria for Adverse Events, version 4.ResultsMost of the 54 patients were men (n = 41; 76%), median age was 75 years; stage IA (n = 36; 66%) and adenocarcinoma (n = 43; 80%) were the most common stage and histologic diagnosis, respectively. Five patients had two lung lesions. A median of three fractions (range, 3 to 5 fractions) and a total median dose of 54 Gy (range, 45 to 60 Gy) per lesion were prescribed. The median follow-up was 17.8 months (range, 4 to 56.4 months). The 2-year rates of LC, regional or distant failure-free survival, and OS were 89.1% (95% CI, 72.2% to 96%), 79% (95% CI, 59.8% to 89.8%), and 80% (95% CI, 64% to 89.8%), respectively. Grade 3 to 4 toxicities were observed in two patients (3%): grade 3 pneumonitis (n = 1) and grade 4 skin toxicity (n = 1).ConclusionSBRT results in high rates of 2-year LC, regional or distant failure-free survival, and OS with low rates of severe toxicity in patients with inoperable primary NSCLC disease.

Intensity modulated radiation therapy and surgery for Management of Retroperitoneal Sarcomas: a single-institution experience

BackgroundPeri-operative radiation of retroperitoneal sarcomas (RPS) is an important component of multidisciplinary treatment. All retrospective series thus far included patients treated with older radiation therapy (RT) techniques including 2D and 3DRT. Intensity modulated radiation therapy (IMRT) allows for selective dose escalation while sparing adjacent organs. We therefore report the first series of patients with RPS treated solely with IMRT, surgery and chemotherapy. We hypothesized that IMRT would permit safe dose escalation and superior rates of local control (LC) in this high-risk patient population.MethodsThirty patients with RPS treated with curative intent between 2006 and 2015 were included in this retrospective study. RT was administered either pre- or post-operatively and IMRT was used in all patients. Statistical comparisons, LC, distant metastasis (DM), and overall survival (OS) were calculated by Kaplan-Meier analysis and univariate Cox regression.ResultsMedian follow-up time after completion of RT was 36 months (range 1.4-112). Median tumor size was 14 cm (range 3.6 - 28 cm). The most prevalent histologies were liposarcoma in 10 (33%) patients and leiomyosarcoma in 10 (33%) with 21 patients (70%) having high-grade disease. Twenty-eight (93%) patients had surgical resection with 47% having positive margins. Chemotherapy was administered in 9 (30%) patients. RT was delivered pre-operatively in 11 (37%) patients, and post-operatively in 19 (63%) with 60% of patients receiving a simultaneous integrated boost. Pre-operative median RT dose to the high-risk area was 55 Gy (range, 43–66 Gy) while median post-operative dose was 60.4 Gy (range, 45-66.6 Gy). There was one acute grade 3 and one late grade 3 toxicity and no grade 4 or 5 toxicities. Three year actuarial LC, freedom from DM, and OS rates were 84%, 64%, and 68% respectively. Positive surgical margins were associated with a higher risk of local recurrence (p = 0.02) and decreased OS (p = 0.04). Pre-operative RT was associated with improved LC (p = 0.1) with a 5-year actuarial LC of 100%. Administration of chemotherapy, timing of RT, histology or grade was not predictive of OS.ConclusionsPatients with RPS treated with peri-operative IMRT at our institution had excellent local control and low incidences of toxicity.