Significant Predictor Of Local Control Research Articles

A retrospective study of clinical outcomes for patients with esophageal cancer who were treated with radiotherapy alone

Introduction: Patients with esophageal cancer who are in a poor general condition receive radiotherapy alone, but outcomes are often unsatisfactory. The aim of this study was to clarify recent outcomes of radiotherapy alone for esophageal cancer. Methods: Patients who underwent 50 Gy or more of radiotherapy without chemotherapy were retrospectively reviewed. Endpoints were overall survival (OS), disease-specific survival (DSS), local control (LC), and progression-free survival (PFS). Survival curves were drawn using the Kaplan-Meier method and predictors were analyzed using the Cox proportional hazards model. Results: Sixty-nine patients were included. The median follow-up period was 17.9 months. The 5-year OS, DSS, LC, and PFS rates were 33.2%, 49.8%, 46.2%, and 16.8%, respectively. In the multivariate Cox proportional hazard model, clinical stage was a significant predictor for OS (hazard ratio [HR]: 4.42, 95% confidence interval [CI]: 1.80 – 11.17, p = 0.001), DSS (HR: 2.08, 95% CI: 1.43 – 3.12, p = 0.0001), LC (HR: 1.86, 95% CI: 1.28 – 2.74, p = 0.001), and PFS (HR: 1.65, 95% CI: 1.25 – 2.18, p = 0.0004). Radiation dose was a significant predictor for LC (HR: 0.87, 95% CI: 0.78 – 0.97, p = 0.018) and tumor location was a significant predictor for PFS (HR: 1.55, 95% CI: 1.10 – 2.19, p = 0.018). In subgroup analysis, the 5-year OS, DSS, LC, and PFS rates for stage I were 60.0%, 80.0%, 71.9%, and 46.1%, respectively. Conclusions: Stage, radiation dose and tumor location are significant predictors for outcomes. Patients with stage I esophageal cancer can be cured by radiotherapy alone.

Palliative Quad Shot Radiation Therapy with or without Concurrent Immune Checkpoint Inhibition for Head and Neck Cancer.

Patients with recurrent and metastatic head and neck cancer (HNC) have limited treatment options. 'QuadShot' (QS), a hypofractionated palliative radiotherapy regimen, can provide symptomatic relief and local control and may potentiate the effects of immune checkpoint inhibitors (ICIs). We compared outcomes of QS ± concurrent ICIs in the palliative treatment of HNC. We identified patients who received ≥three cycles of QS from 2017 to 2022 and excluded patients without post-treatment clinical evaluation or imaging. Outcomes for patients who received QS alone were compared to those treated with ICI concurrent with QS, defined as receipt of ICI within 4 weeks of QS. Seventy patients were included, of whom 57% received concurrent ICI. Median age was 65.5 years (interquartile range [IQR]: 57.9-77.8), and 50% patients had received prior radiation to a median dose of 66 Gy (IQR: 60-70). Median follow-up was 8.8 months. Local control was significantly higher with concurrent ICIs (12-month: 85% vs. 63%, p = 0.038). Distant control (12-month: 56% vs. 63%, p = 0.629) and median overall survival (9.0 vs. 10.0 months, p = 0.850) were similar between the two groups. On multivariable analysis, concurrent ICI was a significant predictor of local control (HR for local failure: 0.238; 95% CI: 0.073-0.778; p = 0.018). Overall, 23% patients experienced grade 3 toxicities, which was similar between the two groups. The combination of QS with concurrent ICIs was well tolerated and significantly improved local control compared to QS alone. The median OS of 9.4 months compares favorably to historical controls for patients with HNC treated with QS. This approach represents a promising treatment option for patients with HNC unsuited for curative-intent treatment and warrants prospective evaluation.

Pre-Brachytherapy Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) Response as Predictor of Local Control in the Definitive Treatment of Cervical Cancer

Chemoradiation consisting of external beam radiotherapy (EBRT) followed by brachytherapy (BT) is the standard of care for Stage IB2-IVA cervical cancer (CC). Multi-parametric MRI (mpMRI) is a valuable tool for initial staging, treatment planning and response assessment. In this study, we aim to explore the potential of mpMRI, in particular DW-MRI, to predict overall tumor control following chemoradiation in CC. We identified 78 consecutive patients treated with chemoradiation for FIGO IB2-IVA CC between 2012-2020, who had an MRI at baseline (MRb) and post-EBRT prior to brachytherapy boost (MRpb) that included DW-MRI (b-value = 0 and 800 s/mm2). Median age was 53 years, most patients had squamous cell carcinoma (76.9%) and advanced-stage disease (56.4% stage IIIA-IVA). Median time from completion of EBRT to MRpb was 3 days. Regions of interest (ROI) in primary tumor were delineated on DW image (b = 0 s/mm2) using ITK-SNAP software. DW-MRI data were fitted to a monoexponential model to calculate apparent diffusion coefficient (ADC) values using in-house software platform (MRI-QAMPER). MRpb mean ADC values (n = 78) and relative changes (%) in mean ADC values between MRb and MRpb (n = 64) were correlated with outcomes, including local failure (LF), regional or distant failure (RDF), and failure at any site (FAS), with death without failure as a competing risk. Median follow-up time was 45 months (95% CI 38, 53). At first post treatment assessment, 72 patients (92.3%) had a complete response (CR) in the cervix and 68 patients (87.2%) had CR in all disease sites. Of patients who had CR in the cervix (n = 72), only 1 patient had local recurrence. Of patients who had CR in all disease sites, 10 later recurred (1 LF only, 1 LF&RDF, 8 RDF only). Overall, 7 patients (9%) had LF, and 19 patients (24.4%) had FAS. A higher mean ADC value in MRpb was associated with LF (HR 4.3, 95% CI 1.32, 14.6; P = 0.016), but not with RDF (P = 0.4) or FAS (P = 0.5). A higher relative change in the mean ADC value between MRb and MRpb was associated with a lower risk of LF (HR 0.94, 95% CI 0.90, 0.98; P = 0.002), but not with RDF (P = 0.8) or FAS (P = 0.4). Treatment response as measured on prebrachytherapy DW-MRI is a significant predictor of local control in patients undergoing chemoradiation for stage IB2-IVA CC. ADC values, a quantitative imaging biomarker on MRpb may be instrumental in dose intensification/de-escalation efforts in CC.

Frameless Cobalt60-Based Hypofractionated Stereotactic Radiosurgery (HSRS) for Brain Metastases: Impact of Dose and Volume

<h3>Purpose/Objective(s)</h3> Frameless, gated, image-guided, Cobalt⁶⁰-based hypofractionated stereotactic radiosurgery (Co⁶⁰-HSRS) is a novel technical paradigm in the treatment of brain metastases that allows for both the dosimetric benefits of the Co⁶⁰ based stereotactic radiosurgery (SRS) platform as well as the biologic benefits of fractionation. We report mature local control (LC) and adverse radiation effects (ARE) outcomes following 5 fraction Co⁶⁰-HSRS for intact brain metastases. <h3>Materials/Methods</h3> All patients with intact brain metastases treated with 5-fraction Co⁶⁰-HSRS between 2017-2020 were retrospectively reviewed. Patients were typically selected for HSRS as opposed to single fraction SRS if the metastases were larger (>2cm diameter), were in eloquent areas, or were in proximity to another lesion receiving HSRS. Survival estimates were determined per patient using Kaplan Meier methods, and LC as well as symptomatic ARE rates were determined per lesion using competing risk methods. Univariable competing risk regression using Fine and Gray's methods were performed, and subsequent multivariable (MVA) regression using a backwards step-wise selection technique generated the final adjusted models. <h3>Results</h3> In total 299 metastases in 146 patients were identified. The median clinical and radiologic follow-up was 10.6 (range 0.5-49.9) and 10.7 months (range 0.5-47.6), respectively. The median maximum tumor diameter and volume were 1.7 cm (range, 0.2-3.9 cm) and 2.38 cc (range, 0.004-24.92 cc), respectively. The median total dose and prescription isodose was 27.5 Gy (range, 20-27.5 Gy) in 5 daily fractions and 52% (range, 45%-93%), respectively. The median overall survival (OS) was 12.7 months and the 1-year LC rate was 85%. MVA identified a total dose of 27.5 Gy vs. ≤25 Gy (hazard ratio [HR] 0.59, p = 0.042), and prior chemotherapy exposure (HR 1.99, p = 0.015), as significant predictors of LC. The 1-year ARE rate was 10.8% and the symptomatic ARE rate was 1.8%. MVA identified a gross tumor volume of ≥4.5cc (HR 7.29, p < 0.001) and a mean intra-tumoral dose of ≥39 Gy (HR 3.17, p = 0.034) as significant predictors of symptomatic ARE. <h3>Conclusion</h3> Moderate total doses in 5 daily fractions of Co⁶⁰-HSRS were associated with high rates of LC and a low incidence of symptomatic ARE. A prescription dose of 27.5 Gy was superior with respect to local control versus ≤25 Gy in 5 daily fractions. Target volumes of 4.5cc or larger as well as mean dose >39 Gy, were associated with higher rates of symptomatic necrosis. Further study will help refine the optimal dosimetric constraints for Co⁶⁰-HSRS.

Toxicity and time lapse between immunotherapy and stereotactic radiotherapy of brain metastases

PurposeStereotactic radiotherapy (SRT) is the standard treatment for brain metastases of non-small-cell lung cancer (NSCLC) and melanoma, mostly in combination with immunotherapy. The objective was to retrospectively evaluate the influence of the time-lapse between immunotherapy and stereotactic radiotherapy on toxicity. Patients and methodsFrom 2016 to 2019, 59 patients treated with SRT for 103 brain metastases of NSCLC (60%) and melanoma (40%) in combination with concomitant immunotherapy (≤30 days) were included. The prescribed dose was 20Gy/1f or 33Gy/3f at the isocentre and 14Gy or 23.1Gy (70%) respectively at the PTV envelope (PTV=GTV+2mm). The mean tumour diameter was 14mm (4–52mm). The immunotherapies used were anti-PD1 and anti-PDL1. The 103 metastases were classified into 3 groups according to the time-lapse between instatement of immunotherapy and instatement of SRT for the patient concerned: 7 (7%) in group A (≤7 days), 38 (37%) in group B (7 to 14 days) and 58 (56%) in group C (14 to 30 days). ResultsThe mean follow-up was 10.1 months. The median overall survival was 11.5 months for NSCLC and 12.5 months for melanoma. The percentage of local control (LC) at one year was 65.1% (93.6% for NSCLC and 26.5% for melanoma). The time-lapse between immunotherapy and SRT was not a significant predictor of LC (P=0.86), while the histology was (P<0.001). The proportion of grade≥3 toxicities was 5.1%, and that of radionecrosis was 9.7% (among these patients, 80% were non-symptomatic): 0%, 13.1% and 8.6% for groups A, B and C respectively. The time-lapse between immunotherapy and SRT was not a significant predictor of toxicity. Only tumour volume was a significant predictive factor (P=0.03). ConclusionThe time lapse between immunotherapy and SRT does not influence brain toxicity. The tumour volume remains the main factor.

Biologically effective dose and overall survival in stereotactic body radiotherapy for lung tumors

Stereotactic body radiotherapy (SBRT) delivers precise concentric radiation to a tumor. It is well established that local control depends on the biologically effective dose (BED) delivered, with BED10 of ≥100 as a significant predictor of local control. The aim of this study was to evaluate factors associated with overall survival (OS) in inoperable lung cancer cases treated with SBRT. From 2013 to 2016, 22 patients with inoperable lung cancer treated with SBRT who could be followed up until their time of death were retrospectively enrolled. Data on sex, age, dose (Gray), number of fractions, BED (α/β = 10), pathology, tumor location, performance status, and background lung disease were collected. The median total dose at the isocenter was 50 Gy, and median BED was 120 Gy. OS was compared in groups with BED of ≥120 Gy (“high-BED”; n = 15) and BED of <120 Gy (“low-BED,” n = 7). Overall, 1‑year OS was 48%. In the univariate analysis, the number of fractions, BED, and pathology were significantly associated with OS. The high-BED group showed better OS, with 1‑ and 2‑year OS of 64% and 21%, respectively, compared with 25% and 0%, respectively, for the low-BED group (p = 0.04). No adverse event of grade 3 or higher occurred. For these inoperable lung cancer cases treated with SBRT, BED was significantly associated with OS. The poor OS rate observed in this case series might be associated with the fact that all the tumors were inoperable.

Local Tumor Control for Metastatic Epidural Spinal Cord Compression Following Separation Surgery with Adjuvant CyberKnife Stereotactic Radiotherapy or Image-Guided Intensity-Modulated Radiotherapy

We sought to compare local tumor control after conventionally fractionated image-guided intensity-modulated radiotherapy (IMRT) versus adjuvant CyberKnife stereotactic body radiotherapy (SBRT) in patients who underwent separation surgery for metastatic epidural spinal cord compression (MESCC). We retrospectively reviewed patients with MESCC who were treated at our hospital. The Kaplan-Meier method was used to estimate local progression and overall survival. Fifty-six patients with MESCC underwent separation surgery between 2013 and 2018, among whom 6 were lost to follow-up, 24 received conventionally fractionated image-guided IMRT, and 26 were treated with CyberKnife SBRT. The median follow-up was 16.5 months (range, 2.1-47.5 months). Eleven patients experienced local failure including 9 and 2 from the IMRT and SBRT groups, respectively. The local progression-free survival rates were significantly higher in the SBRT group than IMRT group at 6 months (95.5% vs. 82.0%), 1 year (90.9% vs. 71.8%), and 2 years (90.9% vs. 57.6%) (P = 0.035). Multivariate Cox proportional hazards regression analysis identified radiotherapy method (P = 0.034) and receipt of preoperative radiotherapy (P = 0.047) as significant predictors of local control, while visceral metastasis (P = 0.048) and high-malignancy primary tumor type (P = 0.002) were negative predictors of overall survival. Moreover, postoperative SBRT was noninferior to IMRT in terms of pain control, adverse effects, and performance in treating irradiated spinal metastases. Hybrid surgery-radiosurgery therapy is a safe and effective treatment option for patients with MESCC. SBRT provided higher local control rates compared with IMRT. Thus postoperative SBRT should be considered for patients expected to have relatively long survival.

Hypofractionated Radiation Therapy for Unresectable/Locally Recurrent Intrahepatic Cholangiocarcinoma

To evaluate outcomes for patients with unresectable/locally recurrent intrahepatic cholangiocarcinoma (ICC) treated with hypofractionated proton or photon radiation therapy (HF-RT). We retrospectively identified 66 patients with ICC who were treated with HF-RT from 2008-18. 51 patients had intrahepatic disease only, and 15 patients had extrahepatic disease at time of RT but received RT for biliary control. Median age at RT was 76 years (range: 30-92), including 27 patients (41%) ≥ 80 years. Median RT dose was 58.05 Gy (range: 37.5-67.5), all delivered in 15 daily fractions. 32 patients received proton RT, and 34 patients received photon RT. Rates of local control (LC), progression-free survival (PFS), and overall survival (OS) were calculated with the Kaplan-Meier method. Univariate and multivariate analyses were conducted using the Cox proportional hazards method. For multivariate analyses, variables with p < 0.5 on univariate analysis were evaluated by backwards selection. Median follow-up times from diagnosis and RT start were 21 months and 14 months, respectively. In total, 5 patients (7.6%) developed local failure. Only 1 patient developed isolated local failure. The 2-yr outcomes were 93% LC, 37% PFS, and 55% OS. Among the 51 patients treated with definitive intent, the 2-yr LC was 96%, PFS 35%, OS 60%. Receipt of protons was significantly associated with younger age (p = 0.02), but not gender, race, ECOG status, metastatic disease at presentation, mean liver dose, cumulative GTV, or number of lesions. There were no significant predictors of LC or PFS, including RT dose. On UVA for OS, younger age, female gender, prior chemotherapy, and prior surgery were significantly associated with improved OS (p < 0.05). On MVA, female gender (HR: 0.33, p = 0.001), prior chemotherapy (HR: 0.38, p = 0.002), and proton vs. photon RT (HR: 0.50, p = 0.05) remained significantly associated with OS. The rate of overall Grade 3+ toxicity was 11%. Radiation-induced liver disease (RILD) was documented in 1 patient who underwent glucocorticoid treatment. HF-RT yields high rates of local control and is an effective modality to optimize biliary control for unresectable/locally recurrent ICC. HF-RT is well tolerated and should be considered as a treatment option for elderly patients who are considered medically inoperable. Proton RT and chemotherapy may further improve outcomes.

The Effect of the Time Interval Between Radiation and Hyperthermia on Clinical Outcome in 400 Locally Advanced Cervical Carcinoma Patients.

Background: Addition of deep hyperthermia to radiotherapy results in improved local control (LC) and overall survival compared to radiotherapy alone in cervical carcinoma patients. Based on preclinical data, the time interval between radiotherapy, and hyperthermia is expected to influence treatment outcome. Clinical studies addressing the effect of time interval are sparse. The repercussions for clinical applications are substantial, as the time between radiotherapy and hyperthermia should be kept as short as possible. In this study, we therefore investigated the effect of the time interval between radiotherapy and hyperthermia on treatment outcome.Methods: We analyzed all primary cervical carcinoma patients treated between 1996 and 2016 with thermoradiotherapy at our institute. Data on patients, tumors and treatments were collected, including the thermal dose parameters TRISE and CEM43T90. Follow-up data on tumor status and survival as well as late toxicity were collected. Data was analyzed using Cox proportional hazards analysis and Kaplan Meier analysis.Results: 400 patients were included. Kaplan Meier and univariate Cox analysis showed no effect of the time interval (range 30–230 min) on any clinical outcome measure. Besides known prognostic factors, thermal dose parameters TRISE and CEM43T90 had a significant effect on LC. In multivariate analysis, the thermal dose parameter TRISE (HR 0.649; 95% CI 0.501–0.840) and the use of image guided brachytherapy (HR 0.432; 95% CI 0.214–0.972), but not the time interval, were significant predictors of LC and disease specific survival.Conclusions: The time interval between radiotherapy and hyperthermia, up to 4 h, has no effect on clinical outcome. These results are re-ensuring for our current practice of delivering hyperthermia within maximal 4 h after radiotherapy.

Hypofractionated radiation therapy for unresectable/locally recurrent intrahepatic cholangiocarcinoma.

412 Background: Our objective was to evaluate outcomes for patients with unresectable/locally recurrent intrahepatic cholangiocarcinoma (ICC) treated with hypofractionated proton or photon radiation therapy (HF-RT). Methods: We retrospectively identified 66 patients with ICC who were treated with HF-RT from 2008-18. 51 patients had intrahepatic disease only, and 15 patients had extrahepatic disease at time of RT but received RT for biliary control. Median age at RT was 76 years (range: 30-92), including 27 patients (41%) ≥ 80 years. Median RT dose was 58.05 Gy (range: 37.5-67.5), delivered in 15 daily fractions. 32 patients received proton RT, and 34 patients received photon RT. Rates of local control (LC), progression-free survival (PFS), and overall survival (OS) were calculated by the Kaplan-Meier method. Univariate and multivariate analyses were conducted using the Cox proportional hazards method. For multivariate analyses, variables with p &lt; 0.5 on univariate analysis were evaluated by backwards selection. Results: Median follow-up times from diagnosis and RT start were 21 and 14 months, respectively. In total, 5 patients (7.6%) developed local failure. Only 1 patient developed isolated local failure. The 2-yr outcomes were 93% LC, 37% PFS, and 55% OS. Among the 51 patients treated with definitive intent, the 2-yr LC was 96%, PFS 35%, OS 60%. Receipt of protons was significantly associated with younger age (p = 0.02), but not gender, race, ECOG status, metastatic disease at presentation, mean liver dose, cumulative GTV, or number of lesions. There were no significant predictors of LC or PFS, including RT dose. On UVA for OS, younger age, female gender, prior chemotherapy, prior surgery, and proton RT were associated with improved OS (p &lt; 0.05). On MVA, female gender (HR: 0.33, p = 0.001), prior chemotherapy (HR: 0.38, p = 0.002), and proton vs. photon RT (HR: 0.50, p = 0.05) remained significantly associated with OS. Conclusions: HF-RT yields high rates of local control and is an effective modality to optimize biliary control for unresectable/locally recurrent IC. HF-RT should be considered for elderly patients who are considered medically inoperable. Proton RT and chemotherapy may further improve outcomes.

Preradiotherapy Tumor Volume in Local Control of Squamous Cell Carcinoma of the Supraglottic Larynx

Examine the utility of pretreatment computed tomography in predicting local control (LC) in squamous cell carcinoma of the supraglottic larynx treated with primary radiotherapy (RT). In total, 167 patients treated between 1983 and 2013 were reviewed. Patients had received pretreatment diagnostic computed tomographic imaging of the larynx and neck from which primary tumor volume (PrTV) was delineated. LC, larynx function at last follow-up, and RT complications were recorded. PrTV was evaluated with respect to outcome. In this study, median age was 61 years, and mean follow-up was 96 months. In total, 43% had T1-T2, 46% had T3, and 11% had T4 disease; 49% had N0 disease. Median tumor volume, 5.1 cm (0.4 to 188 cm). Mean dose, 74 Gy; 20% received concurrent chemotherapy. Overall, 10-year LC was 78.9%. Ten-year LC stratified by tumor volume was: 0 to 4.9 cm, 90.8%; 5 to 8.9 cm, 67.3%; and >9 cm, 69.4%. Ten-year LC with preserved larynx function was: 0 to 4.9 cm, 76.7%; 5 to 8.9 cm, 61.5%; and >9 cm, 53.4%. LC and LC with preserved larynx function was significantly different between PrTV groups (P<0.001). On multivariate analysis, PrTV was a significant predictor of LC and LC with preserved larynx function (P<0.005). Six patients developed soft tissue necrosis; 2 suffered fatal carotid blowouts. Patients with grade 5 complications received concomitant chemotherapy. Four patients required total laryngectomy; 14 required permanent tracheostomy or gastrostomy tube. Pretreatment PrTV helps identify patients most likely to experience LC with primary RT alone or combined chemoradiation. LC for supraglottic larynx squamous cell carcinoma is optimal if the PrTV is <5.0 cm.

Predictive Factors for Local Control and Survival in Patients with Cancer of Unknown Primary (CUP) Irradiated for Cerebral Metastases.

To identify predictors of local control and survival after whole-brain irradiation (WBI) for cerebral metastases from cancer of unknown primary (CUP). In 140 patients receiving WBI alone or following resection, seven factors were investigated including treatment approach, WBI-regimen, age, gender, Eastern Cooperative Oncology Group (ECOG) performance score, number of cerebral lesions and extra-cerebral metastases. On univariate analysis, resection plus WBI and boost (p=0.002), ECOG 0-1 (p<0.001) and a single lesion (p<0.001) were positively associated with local control. On Cox regression, ECOG-score remained significant (p=0.002). On univariate analysis of survival, surgery plus WBI and boost (p=0.009), ECOG 0-1 (p<0.001), a single lesion (p=0.024) and no extra-cerebral metastases (p<0.001) were associated with better outcomes. On Cox regression, ECOG-score (p<0.001) and extra-cerebral lesions (p<0.001) were significant. Significant predictors of local control and survival were identified that contribute to treatment personalization and design of prospective trials in patients with cerebral metastases from CUP.

Pre-radiation Therapy Tumor Volume as a Predictor of Local Control in Squamous Cell Carcinoma of the Supraglottic Larynx: A 30-Year Experience

To examine the utility of pretreatment CT in predicting local control (LC) in patients with squamous cell carcinoma (SCC) of the supraglottic larynx treated with primary radiation therapy (RT). 167 patients treated with primary RT for supraglottic larynx SCC between 1983 and 2013 were reviewed. Patients had received pretreatment diagnostic CT imaging of the larynx and neck with intravenous contrast from which the primary tumor volume was delineated. The mean dose was 74 Gy; 20% received concurrent chemotherapy. LC, larynx function at last follow-up, and RT complications were recorded. Tumor volume was evaluated with respect to outcome. Median age, 61 years. Mean follow-up, 96 months. Of these, 43% had T1-T2, 46% had T3, and 11% had T4 disease; 49% had N0 disease. Median tumor volume, 5.1cm3 (0.4-188 cm3). The 10-year LC for the entire patient population was 78.9%. LC at 5 and 10 years was stratified by tumor volume: 0-4.9 cm3, 5-8.9 cm3, and 9 cm3 and greater. LC by tumor volume among all patients at 10 years were as follows: 0-4.9 cm3, 90.8%; 5-8.9 cm3, 67.3%; and 9 cm3 and greater, 69.4%. LC with preserved larynx function by tumor volume at 10 years was as follows: 0-4.9 cm3, 76.7%; 5-8.9 cm3, 61.5%; and 9 cm3 and greater, 53.4% LC and LC with preserved larynx function was significantly different between primary tumor volume groups (P < .001). On multivariate analysis, primary tumor volume was the only significant predictor of LC and LC with preserved larynx function (P < .005). T stage, N stage, pre-RT larynx dysfunction, chemotherapy, and RT dose did not significantly influence outcome. Six patients developed soft-tissue necrosis; 2 suffered fatal carotid blowouts. Patients with grade 5 complications were treated with concomitant chemotherapy. Four patients required total laryngectomy for a non-functional larynx; 14 required permanent tracheostomy or gastrostomy tube. Pretreatment primary tumor volume helps identify patients most likely to experience LC with primary RT alone or combined chemoradiation. LC for supraglottic larynx SCC is optimal if the primary tumor volume is <5.0cm3.

Response of Oligometastatic Non–Small Cell Lung Cancer to the Adrenal Gland Treated with Stereotactic Body Radiosurgery

Stereotactic body radiation therapy (SBRT) delivers high-dose hypofractionated radiation precisely to a particular site of cancer. The results of SBRT on local control for patients with oligometastatic Non-Small Cell Lung Cancer (NSCLC) with adrenal metastases were analyzed in this prospective study. Data from all consecutive patients with oligometastatic NSCLC to the adrenal gland were prospectively evaluated. Twenty-six adrenal metastases from NSCLC (19 adenocarcinoma, 4 squamous cell carcinoma, 2 bronchogenic carcinoma and 1 large cell carcinoma) were treated in 23 individuals. Age at treatment ranged from 42 – 77 years (mean 62) with 13 men and 10 women. Two patients had bilateral adrenal metastases. Tumor volumes ranged from 2.7 – 168 cc (mean 44.2 cc) and were treated with 500 – 900cGy per fraction, in 5 – 8 fractions, to a cumulative dose of 2,500 – 4,500cGy (mode 4,000cGy). Cancers were followed with MRI, CT and PET scans. Tumor control was defined as cessation of growth, shrinkage, or disappearance of the treated cancer. At analysis, follow-up ranged from 1 – 53 months (mean 10 months). There was an overall 88% control rate for NSCLC. Univariate logistic regression of tumor response showed that histology, age, total dose, pre-treatment volume, and gender were not significant predictors of local control. One patient with progression of both their adrenal metastases initially had tumor regression, but progressed as their primary disease subsequently grew. Another patient with tumor growth following SBRT underwent re-irradiation which continued to provide tumor control at last follow-up (30 months). The treatments were generally well tolerated without significant adverse events. In our experience, SBRT for oligometastatic NSCLC in the adrenal gland provides a safe, non-invasive treatment modality with a high rate of local tumor control. Patients with oligometastatic lung cancer treated to adrenal gland metastases continue to be evaluated for longer follow-up in order to determine if controlling the extrathoracic disease translates to a progression free and overall survival benefit.

Early-Stage Lung Adenocarcinoma Treated With Stereotactic Body Radiation Therapy: Prognostic Factors for Treatment Outcomes

While stereotactic body radiotherapy (SBRT) has been well-established as an effective treatment for early-stage lung cancer, follow-up studies have suggested that the incidence of regional recurrence and distant metastasis can be significant. Given that the histologic subtype of lung adenocarcinoma on either surgical or core biopsy specimens has been recognized as a prognostic factor, we sought to evaluate outcomes after SBRT for early-stage lung adenocarcinoma based on this variable. A review of institutional registries identified 51 consecutive patients (55 lesions) with stage I to IIA lung adenocarcinoma who had undergone definitive SBRT at our institution from August 2009 to August 2016. Potentially prognostic indicators including International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) histologic subtypes of lung adenocarcinoma, positron emission tomography (PET) parameters of maximal standardized uptake value (SUVmax), PET volume (volume at 40% of SUVmax), PET volume multiply SUVmax and TLG (total lesion glycolysis), T stage and the pattern of initial presentation (uni- versus multi-focal) as well as pre-SBRT history of malignancy were analyzed to determine if there was an association with local, nodal, regional, distant failure and overall survival rates using logistic regression models. The median follow-up for the entire cohort was 2.17 years. The failure rates of local, nodal, regional, and distant were 5.6%, 19.2%, 25.9% and 24.5%, respectively. The overall survival rate was 71.2%. The PET parameters volume, volume times maximal SUV and TLG as well as T stage (T3 above) were identified as significant predictors (p<0.05) for local control. Any pre-SBRT history of malignancy was significantly associated with higher incidence of distant metastasis. The histologic subtype of adenocarcinoma and presentation of multi-focal lesions were not associated with treatment outcomes (p>0.05, for all). We demonstrated that volume of PET and T stage were significant predictors of local control after SBRT for early-stage adenocarcinoma of the lung. A history of prior malignancy was associated with a high incidence of distant metastasis. We are unable to identify histologic subtype of adenocarcinoma and multi-focal lesions at presentation as prognostic factors.

Clinical utility of texture analysis of 18F-FDG PET/CT in patients with Stage I lung cancer treated with stereotactic body radiotherapy.

We evaluated the reproducibility and predictive value of texture parameters and existing parameters of 18F-FDG PET/CT images in Stage I non-small-cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT). Twenty-six patients with Stage I NSCLC (T1-2N0M0) were retrospectively analyzed. All of the patients underwent an 18F-FDG PET/CT scan before treatment and were treated with SBRT. Each tumor was delineated using PET Edge (MIM Software Inc., Cleveland, OH), and texture parameters were calculated using open-source code CGITA. From 18F-FDG PET/CT images, three conventional parameters, including maximum standardized uptake value (SUV), metabolic tumor volume (MTV) and total lesion glycolysis (TLG), and four texture parameters, including entropy and dissimilarity (derived from a co-occurrence matrix) and high-intensity large-area emphasis (HILAE) and zone percentage (derived from a size-zone matrix) were analyzed. Reproducibility was evaluated using two independent delineations conducted by two observers. The ability to predict local control (LC), progression-free survival (PFS) and overall survival (OS) was tested for each parameter. All of the seven parameters except zone percentage showed good reproducibility, with intraclass correlation coefficient values >0.8. In univariate analysis, only HILAE was a significant predictor for LC. Histology, dose fractionation, and maximum SUV were associated with PFS, and histology and dose fractionation were associated with OS. We showed that texture parameters derived from 18F-FDG PET/CT were reproducible and potentially beneficial for predicting LC in Stage I lung cancer patients treated with SBRT.

Using primary tumor volumetry to predict treatment outcome for patients with oropharyngeal cancer who were treated with definitive chemoradiotherapy.

This study aimed to determine predictive values for volumetric measures in patients with oropharyngeal cancer who received definitive chemoradiotherapy (CCRT). Contrast-enhanced computed tomography (CT) scans were obtained before radiotherapy (RT) (I), after delivering a median RT of 50.6 Gy (R) and three months after RT (F). Primary site gross tumor volumes (GTV) were assessed using these scans (GTVI , GTVR and GTVF ). The percentage volume change between GTVI and GTVR (GTV change) was calculated. Volumetric analyses of primary site local control (LC) and progression-free survival (PFS) were performed. In total, 35 patients were evaluated, with a median 31 months of follow-up. The 2-year LC rates (LCRs) were 95.0% for patients with GTVI <23 cc, and 42.9% for those with GTVI ≥23 cc (P = 0.001); the 2-year PFS rates were 85.9% and 21.9% (P = 0.002), respectively. Using GTVR classifications <11 cc or ≥11 cc, log-rank tests demonstrated differences in 2-year LCR (95.2% vs 33.3%, P < 0.001) and 2-year PFS (86.5% vs 0%, P < 0.001). There was no local progression in patients with GTV change ≥75%, and GTV change predicted poor PFS (P = 0.026). On multivariate analysis, GTVR ≥11 cc was a significant predictor of poor LCR (hazard ratio [HR] = 26, P = 0.009) and PFS (HR = 8.33, P = 0.046). For patients with oropharyngeal cancer treated with definitive CCRT, GTVI , GTVR and GTV changes predicted LC and PFS; GTVR was the most significant predictor of LC and PFS. RT intensification should be considered for patients with larger remaining tumors after CCRT.

Outcomes of salvage high-dose-rate brachytherapy with or without external beam radiotherapy for isolated vaginal recurrence of endometrial cancer.

PurposeThis study was designed to retrospectively analyze outcomes of high-dose-rate (HDR) brachytherapy, with or without external beam radiotherapy (EBRT), in patients with vaginal recurrence of endometrial carcinoma, and to identify factors prognostic of patient outcomes.Material and methodsThe medical records of all patients who underwent HDR brachytherapy for initial recurrence in the vagina of endometrial cancer after definitive surgery between 1992 and 2014 were retrospectively reviewed. All patients underwent either intracavitary brachytherapy (ICBT) or interstitial brachytherapy (ISBT) with or without EBRT. Late toxicity was graded using the EORTC (LENT/SOMA) scale, revised in 1995.ResultsThirty-seven patients were identified. The median follow-up time was 48 months (range: 6-225 months). Of these 37 patients, 23 underwent ICBT, 14 underwent ISBT, and 26 underwent EBRT. Tumor size at first examination of initial relapse was significantly larger in the ISBT than in the ICBT group. The 4-year respective overall survival (OS), local control (LC), and progression-free survival (PFS) rates in the entire cohort were 81.0%, 77.9%, and 56.8%, respectively. The interval between diagnosis of first recurrence and radiotherapy (< 3 months, ≥ 3 months) was a significant predictor of LC and PFS. OS and LC rates did not differ significantly in the ICBT and ISBT groups. Two patients experienced grade 2 rectal bleeding, and four experienced grade 2 hematuria. No grade 3 or higher late complications were observed.ConclusionsSalvage HDR brachytherapy is an optimal for treating vaginal recurrence of endometrial carcinoma with acceptable morbidity. Early radiotherapy, including brachytherapy, should be considered for women who experience vaginal recurrence of endometrial cancer.

Duration of Twice-Daily Thoracic Radiotherapy and Time From the Start of Any Treatment to the End of Chest Irradiation as Significant Predictors of Outcomes in Limited-Disease Small-Cell Lung Cancer

BackgroundThe hypothesis of this retrospective study was that the duration of twice-daily (BID) thoracic radiotherapy (TRT) and time from the start of any treatment to the end of chest irradiation (SER) would predict outcomes in limited-disease small-cell lung cancer. Materials and MethodsAll 81 patients received 45 Gy in 30 fractions BID with a ≥ 6-hour interval and concurrent chemotherapy of platinum and etoposide. ResultsThe median radiotherapy duration was 25 days (range, 21-38 days). The 5-year overall survival rates were 26.2% (95% confidence interval [CI], 14.3%-38.0%), and the median survival time was 30 months (95% CI, 15.5-44.5 months). Using multivariate regression analysis, the significant predictors of survival were the sum of the diameters of the primary tumor and metastatic lymph nodes, male gender, age ≥ 60 years, and the duration of BID-TRT (hazard ratio [HR], 1.15; 95% CI, 1.06-1.25; HR, 2.38; 95% CI, 1.13-5.02; HR, 2.38; 95% CI, 1.10-5.17; and HR, 1.08; 95% CI, 1.01-1.15, respectively). A total of 70 of 81 patients (86%) received radiotherapy during the first chemotherapy cycle. The median SER was 29 days (range, 21-109 days). The 5-year local control rate was 48.7% (95% CI, 33.9%-63.6%). The significant predictors of local control were the sum of the diameters of the primary tumor and metastatic lymph nodes, age ≥ 60 years, and SER (HR, 1.18; 95% CI, 1.06-1.31; HR, 4.18; 95% CI, 1.23-14.24; and HR, 1.02; 95% CI, 1-1.04, respectively). ConclusionsThe duration of BID-TRT and SER were identified as one of the significant predictors of survival and local control in limited-disease small-cell lung cancer treated with concurrent chemoradiotherapy at 45 Gy in 30 fractions, respectively.

Impact of pretreatment whole-tumor perfusion computed tomography and 18F-fluorodeoxyglucose positron emission tomography/computed tomography measurements on local control of non-small cell lung cancer treated with stereotactic body radiotherapy.

This study aimed to investigate the correlation between the average iodine density (AID) detected by dual-energy computed tomography (DE-CT) and the maximum standardized uptake value (SUVmax) yielded by [18F] fluorodeoxyglucose positron emission tomography (18F-FDG PET) for non–small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). Seventy-four patients with medically inoperable NSCLC who underwent both DE-CT and 18F-FDG PET/CT before SBRT (50‒60 Gy in 5‒6 fractions) were followed up after a median interval of 24.5 months. Kaplan–Meier analysis was used to determine associations between local control (LC) and variables, including AID, SUVmax, tumor size, histology, and prescribed dose. The median AID and SUVmax were 18.64 (range, 1.18–45.31) (100 µg/cm3) and 3.2 (range, 0.7–17.6), respectively. No correlation was observed between AID and SUVmax. Two-year LC rates were 96.2% vs 75.0% (P = 0.039) and 72.0% vs 96.2% (P = 0.002) for patients classified according to high vs low AID or SUVmax, respectively. Two-year LC rates for patients with adenocarcinoma vs squamous cell carcinoma vs unknown cancer were 96.4% vs 67.1% vs 92.9% (P = 0.008), respectively. Multivariate analysis identified SUVmax as a significant predictor of LC. The 2-year LC rate was only 48.5% in the subgroup of lower AID and higher SUVmax vs >90% (range, 94.4–100%) in other subgroups (P = 0.000). Despite the short follow-up period, a reduction in AID and subsequent increase in SUVmax correlated significantly with local failure in SBRT-treated NSCLC patients. Further studies involving larger populations and longer follow-up periods are needed to confirm these results.