Evaluation of response after SBRT for liver tumors.

Stereotactic body radiotherapy (SBRT) has developed over the last few years for the treatment of primary and metastatic hepatic tumors. The tumoral and adjacent peritumoral modifications caused by this radiosurgery limit the evaluation of response by anatomic imaging and dimensional criteria alone, such as with RECIST. This suggests that it is of interest to also take into account the residual enhancement and hyper metabolism of these hepatic targets. We have reviewed the English language literature regarding the response of hepatic lesions treated by SBRT, and found that only seven articles were specifically concerned with this problem. The response of the hepatocellular carcinoma after SBRT has been studied specifically with multiphase enhanced CT-scan. Criteria set by the European Association of Study of the Liver better estimate response at each time point of follow up than RECIST does. Non-enhancement, reflecting tumor necrosis, is additionally an early indicator of response with extended response in time and a best non-enhancement percentage is observed at 12 months. The response after treatment by SBRT of cholangiocarcinoma has not yet generated a specific report. Use of RECIST criteria is also inadequate in the evaluation of response after SBRT for hepatic metastases. Response of liver metastases to SBRT is better assessed with a combination of size and enhancement pattern. The occurrence of a lobulated enhancement during follow up is efficient to predict local progression in a specific, reproducible, and sensitive way. Patients with FDG-avid hepatic metastases are also better evaluated with PET-CT and functional criteria than routine imaging and metric evaluation alone.

CT-Guided Online Adaptive Radiotherapy Delivered via Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy (PULSAR) for a Bulky Thoracic and Abdominal Mass in Oligometastatic Renal Cell Carcinoma.

In the context of oligometastatic renal cell carcinoma (RCC), local treatment with stereotactic body radiotherapy (SBRT) may improve oncologic outcomes. However, the location and size can often pose a technical challenge in standard SBRT delivery, and the dose is potentially limited by nearby organs at risk (OARs). Online adaptive radiotherapy (oART) improves radiation delivery by personalizing high-dose fractions to account for daily stochastic variations in patient anatomy or setup. The oART process aims to maximize tumor control and enhances precision by tailoring to a more accurate representation of a patient in near-real time. The proceeding re-optimization can mitigate the uncertainty inherent in the traditional radiation delivery workflow and precludes the need for larger margins that account for anatomical variations and setup errors. Here, we describe a case of oligometastatic RCC with a bulky (>300 cm3) pleural-based left lower lobe mass extending into the upper abdomen treated via personalized ultrafractionated stereotactic adaptive radiotherapy (PULSAR). Three fractions were delivered four weeks apart allowing for tumor shrinkage of these bulky lesions, and oART permitted on-table adaptation of the plan without traditional re-simulation and re-planning required during off-line adaptive radiotherapy. The plan was designed for the Ethos linear accelerator (Varian Medical Systems, Inc., Palo Alto, CA, USA). The prescription dose was 36 Gray (Gy) in three fractions, and the adapted plan was selected in each treatment over the scheduled plan due to better target coverage and reversal of OAR dose violations. The adapted plan met all OAR dose constraints, and it achieved higher target coverage in the first two PULSAR fractions compared to the scheduled plan. In the third fraction, the cumulative point dose was approaching the maximum heart tolerance, and target coverage was accordingly compromised based on clinical judgment. There was evidence of tumor regression throughout the course of treatment, and the patient did not develop any significant radiation-related toxicities. Follow-up imaging has demonstrated the overall stable size of her lesion without any evidence of disease progression. Our case reflects the benefit of adaptive SBRT delivery to a bulky mass near multiple OARs in the setting of oligometastatic RCC. The adapted plan allowed for prioritization of critical structures on a fraction-by-fraction basis while preserving the therapeutic intent of SBRT. Further integration of advanced imaging techniques, optimal disease-specific systemic immunotherapies or targeted therapies, and refinement of patient selection will be crucial in identifying which patients would most benefit from an adaptive approach.

SpaceOAR Complication Affecting the Treatment of Prostate Cancer.

A 60-year-old male presented with an elevated prostate-specific antigen (PSA) of 10 ng/ml. A transrectal ultrasound-guided prostate biopsy showed prostate adenocarcinoma GS 4+3 (grade 3) with 5 out of 12 cores positive for malignancy. He initially planned to have prostate stereotactic body radiation therapy (SBRT) with SpaceOAR gel insertion in his rectoprostatic space to reduce radiation to the rectum. Magnetic resonance imaging (MRI) two months after SpaceOAR insertion showed evidence of infiltration of the SpaceOAR within the anterior rectal wall. This delayed his treatment and he was started on a short course of androgen deprivation therapy with Leuprolide while waiting for absorption of the gel. After completion of androgen deprivation therapy, the patient was treated with external beam radiation therapy (EBRT) to the prostate, seminal vesicles, and pelvis to a total dose of 6000 centigray (cGy) in 20 fractions at a dose per fraction of 300 cGy. He did well after treatment with minimal side effects.

Inflammatory Myofibroblastic Tumor After Receiving Treatment for Non-small Cell Carcinoma.

Inflammatory pseudotumor encompasses a spectrum of both neoplastic and non-neoplastic conditions characterized by a histological pattern featuring a proliferation of cytologically bland spindle cells, accompanied by a prominent chronic inflammatory infiltrate. Within this spectrum, inflammatory myofibroblastic tumor (IMT) has emerged as a distinct entity over the past two decades, marked by unique clinical, pathological, and molecular characteristics. Typically affecting the visceral soft tissues of children and adolescents, IMT exhibits a propensity for local recurrence while posing a minimal risk of distant metastasis. They are extremely rare in adults, constituting less than 1% of adult lung tumors. Our patient, a 63-year-old female, has an intricate medical background, encompassing chronic obstructive pulmonary disease (COPD), a previous history of smoking (35 pack-years, quit a year before admission), coronary artery disease, non-obstructive hypertrophic cardiomyopathy, and obstructive sleep apnea. Presenting with a diagnostic dilemma, she recently received treatment for non-small cell carcinoma with radiation therapy, which has evolved into a swiftly advancing case of IMT.

Durable Local Control With Preserved Renal Function for Stereotactic Body Radiotherapy in Cryoablation-Refractory Clear Cell Renal Carcinoma.

Renal cell carcinoma (RCC) is the most common type of kidney cancer, accounting for most renal cancers. Oligoprogressive RCC (OP-RCC) describes metastatic RCC wherein one or a few metastatic sites continue to progress, while the majority of metastatic sites are stable on systemic therapy. Treatment options for the primary site for OP-RCC include cytoreductive nephrectomy, stereotactic body radiation therapy (SBRT), or ablative techniques, although there is no currently agreed-upon standard for treatment. This report describes a 76-year-old male with OP-RCC who was treated with salvage SBRT after failing cytoablation therapy. A review of the current literature on SBRT as a treatment option for OP-RCC is presented and discussed. This case demonstrates that SBRT may be a viable salvage treatment option for patients with OP-RCC that provides good local disease control while preserving long-term renal function.

Bothersome Hot Flashes Following Neoadjuvant Androgen Deprivation Therapy and Stereotactic Body Radiotherapy for Localized Prostate Cancer.

BACKGROUND: Androgen deprivation therapy (ADT) improves local cancer control in unfavorable localized prostate cancer treated with radiotherapy. ADT is known to cause hormonally related symptoms that resolve with testosterone recovery. Hot flashes are particularly burdensome. This study sought to evaluate the timeline of hot flashes following short-course ADT and stereotactic body radiotherapy (SBRT) as well as its relationship with testosterone recovery. METHODS: Institutional IRB approval was obtained for this retrospective review of prospectively collected data (IRB#: 2009-510). ADT was initiated three months prior to the start of SBRT. Hot flashes were self-reported via question 13a of the Expanded Prostate Index Composite (EPIC)-26 prior to ADT initiation, the first day of robotic SBRT, and at each follow-up (one, three, six, nine, 12, 18, 24, and 36 months). The responses were grouped into three relevant categories (no problem, very small-small problem, and moderate-big problem). Scores were transformed to a 0-100 scale with higher scores reflecting less bother. Testosterone levels were measured at each follow-up. RESULTS: From 2007 to 2010, 122 localized prostate cancer patients (nine low-, 64 intermediate-, and 49 high-risk according to the D'Amico classification) at a median age of 72 years (range 54.5-88.3) were treated with short course ADT (three to six months) and SBRT (35-36.25 Gy) at Georgetown University Hospital. Thirty-two percent were Black and 27% were obese. Seventy-seven percent of patients received three months of ADT. At baseline, 2% of men experienced hot flashes that were a "moderate to big problem" and that proportion peaked at the start of SBRT (45%) before returning to baseline (2%) nine months post-SBRT with a cumulative incidence of 52.4%. The median baseline EPIC-26 hot flash score of 94 declined to 50 at the start of SBRT but this returned to baseline (92) by six months post SBRT. These changes were both statistically and clinically significant (MID = 9.5083, p<0.01). Testosterone recovery (> 230 ng/dL) occurred in approximately 70% of patients by 12 months post SBRT. Resolution of hot flashes correlated with testosterone recovery. CONCLUSION: Bothersome hot flashes occur in greater than 50% of men treated with neoadjuvant ADT. Resolution of hot flashes occurs in the majority of patients within one year after treatment. Reassurance of the temporary nature of hot flashes may assist in reducing patient anxiety. Measuring testosterone levels at follow-up visits may allow for anticipatory counseling that may limit the associated bother.

Split-Course Adaptive Radioimmunotherapy for Oligometastatic Non-Small Cell Lung Cancer (SiCARIO): A Case Report.

Current treatment paradigms for oligometastatic non-small cell lung cancer (NSCLC) utilize systemic chemotherapy alone or in combination with immune checkpoint inhibitors (ICIs). The addition of ICIs in NSCLC has led to significant improvements in survival; however, recurrence remains common. New methods are needed to enhance anti-tumor immune responses and improve patient outcomes. Here, we present the first case of utilization of the Ethos OART platform to deliver multi-site pulsed hypofractionated radiotherapy in a patient with oligometastatic disease on the single arm prospective clinical trial SiCARIO (Split-Course Adaptive Radioimmunotherapy in Oligometastatic NSCLC, NCT05501665). A 67-year-old man with stage IV NSCLC with metastases to bilateral adrenal glands, retroperitoneum, and mesentery was prescribed treatment of 40 Gy in 5 fractions on SiCARIO in combination with SOC chemoimmunotherapy. A multi-target single isocenter approach was utilized to treat nine distinct targets in five total isocenters. Treatment plans were generated using an isotopic approach prioritizing organ at risk (OAR) constraints with the goal of minimum coverage of at least 30 Gy in 5 fractions. CBCT was acquired with each fraction to generate new targets and OAR contours based on anatomic changes with the patient on the treatment table. A comparison of an adapted plan to a base plan was performed online with a selection of superior plans based on target coverage and OAR constraints. The adapted plan was deemed superior for all but 1 fraction of a single isocenter for this patient. The discussion will focus primarily on the bilateral adrenal isocenter, where bulk tumor shrinkage of greater than 80% was observed in this patient with corresponding significant dosimetric benefits. This case demonstrates a potential clinical benefit of OART in multi-metastasis RT. Further data is needed to confirm the safety and efficacy of this approach. Enrollment is ongoing.

CT-Guided Adaptive Radiotherapy for the Treatment of Technically Challenging Oligometastatic Disease: A Case Report.

There is a growing interest in the application of stereotactic body radiotherapy (SBRT) for the treatment of oligometastatic cancers. This increasing appeal of SBRT has highlighted the need for more sophisticated radiotherapy techniques that allow high doses of radiation to be delivered to multiple sites while limiting the exposure of neighboring healthy tissue. A major obstacle to achieving this aim has been the occurrence of interfraction target variability: the tendency of both the tumor and the surrounding tissue to undergo day-to-day non-synchronous shifts in position. Such changes in the conformation of the tumor field often compromise the effectiveness of conventional SBRT prescribed for a fixed target. We report a case of oligometastatic pelvic disease where the challenge of an unusually mobile tumor was overcome with the use of a novel technique employing cone beam CT (CBCT)-based online adaptive radiotherapy (OART). The Phase I "Adaptive Radiation for Abdominopelvic Metastases (ARAM)" clinical trial was designed to determine if OART can achieve dosing targets superior to those attained using conventional radiotherapy techniques. In this case, CT adaptive planning enabled the treatment of a pelvic target prescribed per protocol to 45Gy that would otherwise have not been amenable to treatment with conventional SBRT planning. Adaptive plans showed significant improvements in target coverage while respecting critical organ constraints, resulting in a total treatment V35Gy of 89.3% and V45Gy of 52.8%, whereas the scheduled plan would have achieved V35Gy of 67.4% and V45Gy of 13.6%. Treatment times were variable (38.1-96.7 mins), and correlated with the magnitude of daily translation which ranged from 4 to 7 cm of total linear translation. The patient tolerated treatment without any adverse events. These results demonstrate a novel application of CBCT-guided OART that allowed for the administration of ablative treatment to an unexpectedly mobile target unamenable to conventional SBRT. CBCT-guided OART currently requires increased treatment time, a need which might be reduced by optimization of daily contouring. The phase 1 clinical trial NCT05880667 is ongoing and may provide further evidence that CBCT-guided OART can meet the technical challenges posed by radiotherapy for oligometastatic abdominal and pelvic disease.

The First Reported Case of Treating the Ultra-Central Thorax With Cone Beam Computed Tomography-Guided Stereotactic Adaptive Radiotherapy (CT-STAR).

Stereotactic body radiotherapy (SBRT) to the central and ultra-central thorax is associated with infrequent but potentially serious adverse events. Adaptive SBRT, which provides more precise treatment planning and inter-fraction motion management, may allow the delivery of ablative doses to ultra-central tumors with effective local control and improved toxicity profiles. Herein, we describe the first reported case of cone beam computed tomography (CBCT)-guided stereotactic adaptive radiotherapy (CT-STAR) in the treatment of ultra-central non-small cell lung cancer (NSCLC) in a prospective clinical trial (NCT05785845). An 80-year-old man with radiographically diagnosed early-stage NSCLC presented for definitive management of an enlarging ultra-central lung nodule. He was prescribed 55 Gy in five fractions with CT-STAR. A simulation was performed using four-dimensional CT, and patients were planned for treatment at end-exhale breath-hold. Treatment plans were generated using a strict isotoxicity approach, which prioritized organ at risk (OAR) constraints over target coverage. During treatment, daily CBCTs were acquired and used to generate adapted contours and treatment plans based on the patient's anatomy-of-the-day, all while the patient was on the treatment table. The initial and adapted plans were compared using dose-volume histograms, and the superior plan was selected for treatment. The adapted plan was deemed superior and used for treatment in three out of five fractions. The adapted plan provided improved target coverage in two fractions and resolved an OAR hard constraint violation in one fraction. We report the successful treatment of a patient with ultra-central NSCLC utilizing CT-STAR. This case report builds on previously published in silico data to support the viability and dosimetric advantages of CT-STAR in the ablative treatment of this challenging tumor location. Further data are needed to confirm the toxicity and efficacy of this technique.

Dynamic tumor-tracking stereotactic body radiotherapy with real-time monitoring of liver tumors using a gimbal-mounted linac: A multi-institutional phase II study.

Background and purpose: This prospective multicenter phase II study aimed to evaluate the safety and efficacy of dynamic tumor tracking (DTT) stereotactic body radiotherapy (SBRT) with real-time monitoring of liver tumors using a gimbal-mounted system. Materials and methods: Patients with < 4 primary or metastatic liver tumors with diameters ≤ 50 mm and expected to have a respiratory motion of ≥ 10 mm were eligible. The prescribed dose was 40 Gy in five fractions. The primary endpoint was local control (LC) at 2 years. The secondary endpoints were overall survival (OS), progression-free survival (PFS), treatment-related toxicity, and tracking accuracy. Results: Between September 2015 and March 2019, 48 patients (48 lesions) with a median age of 74 years were enrolled from four institutions. Of these, 39 were diagnosed with hepatocellular carcinoma and nine with metastatic liver cancer. The median tumor diameter was 17.5 mm. DTT-SBRT was successfully performed in all patients; the median treatment time was 28 min/fraction. The median follow-up period was 36.5 months. The 2-year LC, OS, and PFS rates were 98.0 %, 88.8 %, and 55.1 %, respectively. Disease progression was observed in 33 (68.8 %) patients. One patient (0.2 %) had local recurrence, 31 (64.6 %) developed new hepatic lesions outside the irradiation field, and nine (18.8 %) had distant metastases (including overlap). Grade 3 late adverse events were observed in seven patients (14.5 %). No grade 4 or 5 treatment-related toxicity was observed. The median tracking accuracy was 2.9 mm. Conclusion: Employing DTT-SBRT to treat liver tumors results in excellent LC with acceptable adverse-event incidence.

Comparison of radiofrequency ablation and ablative external radiotherapy for the treatment of intrahepatic malignancies: A hybrid meta-analysis.

Background & Aims: Radiofrequency ablation (RFA) and ablative external beam radiotherapy (ablative RT) are commonly used to treat small intrahepatic malignancies. We meta-analysed oncologic outcomes and systematically reviewed the clinical consideration of tumour location and size. Methods: PubMed, Medline, Embase, and Cochrane Library databases were searched on February 24, 2022. Studies comparing RFA and ablative RT, providing one of the endpoints (local control or survival), and encompassing ≥5 patients in each arm were included. Results: Twenty-one studies involving 4,638 patients were included. Regarding survival, the odds ratio (OR) was 1.204 (p = 0.194, favouring RFA, not statistically significant) among all studies, 1.253 (p = 0.153) among hepatocellular carcinoma (HCC) studies, and 1.002 (p = 0.996) among colorectal cancer metastasis studies. Regarding local control, the OR was 0.458 (p <0.001, favouring ablative RT) among all studies, 0.452 (p <0.001) among HCC studies, favouring the ablative RT arm, and 0.649 (p = 0.484) among colorectal cancer metastasis studies. Pooled 1- and 2-year survival rates for HCC studies were 91.8% and 77.7% after RFA, and 89.0% and 76.0% after ablative RT, respectively; and for metastasis studies were 88.2% and 66.4% after RFA and 82.7% and 60.6% after RT, respectively. Literature analysis suggests that ablative RT can be more effective than RFA for tumours larger than 2-3 cm or for specific sublocations in the liver (e.g. subphrenic or perivascular sites), with moderate quality of evidence (reference to the grading system of the American Society for Radiation Oncology Primary Liver Cancer Clinical Guidelines). The pooled grade ≥3 complication rates were 2.9% and 2.8% in the RFA and ablative RT arms, respectively (p = 0.952). Conclusions: Our study shows that ablative RT can yield oncologic outcomes similar to RFA, and suggests that it can be more effective for the treatment of tumours in locations where RFA is difficult to perform or for large-sized tumours. Systematic Review Registration: This study was registered with PROSPERO (Protocol No: CRD42022332997). Impact and implications: Radiofrequency ablation (RFA) and ablative radiotherapy (RT) are non-surgical modalities for the treatment of small intrahepatic malignancies. Ablative RT showed oncologic outcomes at least similar to those of RFA, and was more effective at specific locations (e.g. perivascular or subphrenic locations).

Patterns of utilization and clinical adoption of 0.35 Tesla MR-guided radiation therapy in the United States - Understanding the transition to adaptive, ultra-hypofractionated treatments.

Purpose/Objective: Magnetic resonance-guided radiation therapy (MRgRT) utilization is rapidly expanding worldwide, driven by advanced capabilities including continuous intrafraction visualization, automatic triggered beam delivery, and on-table adaptive replanning (oART). Our objective was to describe patterns of 0.35Tesla(T)-MRgRT (MRIdian) utilization in the United States (US) among early adopters of this novel technology. Materials/Methods: Anonymized administrative data from all US MRIdian treatment systems were extracted for patients completing treatment from 2014 to 2020. Detailed treatment information was available for all MRIdian linear accelerator (linac) systems and some cobalt systems. Results: Seventeen systems at 16 centers delivered 5736 courses and 36,389 fractions (fraction details unavailable for 1223 cobalt courses), of which 21.1% were adapted. Ultra-hypofractionation (UHfx) (1-5 fractions) was used in 70.3% of all courses. At least one adaptive fraction was used for 38.5% of courses (average 1.7 adapted fractions/course), with higher oART use in UHfx dose schedules (47.7% of courses, average 1.9 adapted fractions per course). The most commonly treated organ sites were pancreas (20.7%), liver (16.5%), prostate (12.5%), breast (11.5%), and lung (9.4%). Temporal trends show a compounded annual growth rate (CAGR) of 59.6% in treatment courses delivered, with a dramatic increase in use of UHfx to 84.9% of courses in 2020 and similar increase in use of oART to 51.0% of courses. Conclusions: This is the first comprehensive study reporting patterns of utilization among early adopters of MRIdian in the US. Intrafraction MR image-guidance, advanced motion management, and increasing adoption of adaptive radiation therapy has led to a substantial transition to ultra-hypofractionated regimens. 0.35 T-MRgRT has been predominantly used to treat abdominal and pelvic tumors with increasing use of on-table adaptive replanning, which represents a paradigm shift in radiation therapy.

Elective nodal radiotherapy with a gapless radiation field junction for oligorecurrent prostate cancer after previous radiotherapy.

Purpose: To evaluate the feasibility of subsequent elective nodal radiotherapy (ENRT) for nodal recurrences after previous radiotherapy with a defined planning approach for a gapless radiation field junction. Methods: Patients with 1) previous radiotherapy of prostate or prostatic fossa and subsequent pelvic ENRT or 2) previous pelvic radiotherapy and subsequent ENRT to paraaortic lymph nodes (LN) and gapless junction of both radiation fields were analyzed. The cumulative maximum dose (Dmax-cum) and the maximum cumulative dose in 1 cc (D1cc-cum) were estimated. Absolute toxicity and the toxicity exceeding baseline were evaluated. Results: Twenty-two patients with PSMA-PET/CT-staged nodal oligorecurrence after prior radiotherapy were treated with pelvic (14 patients) or paraaortic ENRT (9 patients). One patient was treated sequentially at both locations. Median time between first and second RT was 20.2 months. Median doses to the lymphatic pathways and to PET-positive LN were 47.5 Gy and 64.8 Gy, respectively. The planning constraint of an estimated Dmax-cum ≤ 95 Gy and of D1cc-cum < 90 Gy were achieved in 23/23 cases and 22/23 cases, respectively. Median follow-up was 33.5 months. There was no additional acute or late toxicity ≥ grade 3. Worst acute toxicity exceeding baseline was grade 1 in 68.2% and grade 2 in 22.7% of patients. Worst late toxicity exceeding baseline was grade 1 in 31.8% and grade 2 in 18.2% of patients. Conclusion: ENRT for nodal recurrences after a previous radiotherapy with gapless junction of radiation fields seems to be feasible, applying the dose constraints Dmax-cum ≤ 95 Gy and D1cc-cum < 90 Gy without grade 3 acute or late toxicities exceeding baseline.

Stereotactic radiotherapy or metastasectomy for oligometastatic esophagogastric cancer: A nationwide population-based cohort study.

Background and purpose: This nationwide population-based study analyzed the outcomes of local treatment (i.e. stereotactic body radiotherapy [SBRT] or metastasectomy) or systemic therapy for oligometastatic disease (OMD) in patients with esophagogastric cancer in The Netherlands. Materials and methods: Between 2015 and 2016, all patients in The Netherlands with esophagogastric cancer and synchronous or metachronous OMD were eligible for inclusion. Patients who underwent local treatment of OMD (SBRT or metastasectomy) and/or systemic therapy were included. OMD was defined as distant metastases in 1 organ or 1 extra-regional lymph node region. The primary outcomes were overall survival (OS) and independent prognostic factors for OS. OS was calculated from diagnosis of OMD. Prognostic factors for OS were analyzed using a multivariable Cox proportional hazard model. Results: A total of 594 patients were included, of whom 83 underwent local treatment for OMD alone, 22 local treatment plus systemic therapy, and 489 systemic therapy alone. Median OS after local treatment for OMD alone was 16.0 months, local treatment plus systemic therapy 22.7 months, and after systemic therapy alone 8.5 months. Improved OS was independently associated with local treatment for OMD alone or combined with systemic therapy as compared with systemic therapy alone (hazard ratio [HR] 0.52, 95% CI: 0.31-0.90 and HR 0.42, 95% CI: 0.22-0.82, respectively) and a controlled primary tumor(HR 0.48, 95% CI: 0.27-0.86). Worse OS was independently associated with worse performance scores (HR 1.41, 95%: 1.32-1.75), poorly or undiffertumor as compared with good or moderadifferentiated tumor (HR 1.37, 95% CI: 1.06-1.76), and peritoneal as compared with lymph mode metastases (HR 1.39, 95% CI: 1.00-1.93). Conclusion: Local treatment of OMD alone or combined with systemic therapy was independently associated with improved OS as compared with systemic therapy alone in this population-based cohort study in The Netherlands. Randomized controlled trials are warranted to confirm these results.

Statistical evaluation of the effectiveness of dual amplitude-gated stereotactic body radiotherapy using fiducial markers and lung volume.

Background and purpose: The low tracking accuracy of lung stereotactic body radiotherapy (SBRT) risks reduced treatment efficacy. We used four-dimensional computed tomography (4DCT) images to determine the correlation between changes in fiducial marker positions and lung volume for lung tumors, and we evaluated the effectiveness of the combined use of these images in lung SBRT. Materials and methods: Data of 30 patients who underwent fiducial marker placement were retrospectively analyzed. We calculated the motion amplitudes of the center of gravity coordinates of the lung tumor and fiducial markers in each phase and the ipsilateral, contralateral, and bilateral lung volumes using 4DCT. Moreover, we calculated the cross-correlation coefficient between the fiducial marker position and the lung volume changes waveform for the motion amplitude waveform of the lung tumor over three gating windows (all phases, ≤2 mm3, and ≤3 mm3). Results: Compared with the lung volume, approximately 30 % of the fiducial markers demonstrated a low correlation with the lung tumor. In the ≤2 mm3 and ≤3 mm3 gating windows, the cross-correlation coefficients between the lung tumor and the optimal marker (r > 0.9: 83 % and 86 %) were significantly different for all fiducial markers (r > 0.9: 39 %, 53 %) and the ipsilateral (r > 0.9: 35 % and 40 %), contralateral (r > 0.9: 44 % and 41 %), and bilateral (r > 0.9: 39 % and 45 %) lung volumes. Conclusions: Some of the fiducial markers showed a low correlation with the lung tumor. This study indicated that the combined use of lung volume monitoring can improve tracking accuracy.

Prognostic utility of pretreatment neutrophil-lymphocyte ratio in survival outcomes in localized non-small cell lung cancer patients treated with stereotactic body radiotherapy: Selection of an ideal clinical cutoff point.

BACKGROUND AND PURPOSE: Neutrophil-lymphocyte ratio (NLR) has been associated with overall survival (OS) in non-small cell lung cancer (NSCLC). We aimed to assess the utility of NLR as a predictor of lung cancer-specific survival (LCS) and identify an optimal, pretreatment cutoff point in patients with localized NSCLC treated with stereotactic body radiotherapy (SBRT) within the Veterans Affairs' (VA) national database. MATERIALS AND METHODS: In the VA database, we identified patients with biopsy-proven, clinical stage I NSCLC treated with SBRT between 2006 and 2015. Cutoff points for NLR were calculated using Contal/O'Quigley's and Cox Wald methods. Primary outcomes of OS, LCS, and non-lung cancer survival (NCS) were evaluated in Cox and Fine-Gray models. RESULTS: In 389 patients, optimal NLR cutoff was identified as 4.0. In multivariable models, NLR > 4.0 was associated with decreased OS (HR 1.44, p = 0.01) and NCS (HR 1.68, p = 0.01) but not with LCS (HR 1.32, p = 0.09). In a subset analysis of 229 patients with pulmonary function tests, NLR > 4.0 remained associated with worse OS (HR 1.51, p = 0.02) and NCS (HR 2.18, p = 0.01) while the association with LCS decreased further (HR 1.22, p = 0.39). CONCLUSION: NLR was associated with worse OS in patients with localized NSCLC treated with SBRT; however, NLR was only associated with NCS and not with LCS. Pretreatment NLR, with a cutoff of 4.0, offers potential as a marker of competing mortality risk which can aid in risk stratification in this typically frail and comorbid population. Further studies are needed to validate pretreatment NLR as a clinical tool in this setting.

Which Is Better for Liver SBRT: Dosimetric Comparison Between DCAT and VMAT for Liver Tumors.

Stereotactic body radiotherapy (SBRT) is currently well-adopted as a curative treatment for primary and metastatic liver tumors. Among SBRT methods, dynamic conformal arc therapy (DCAT) and volumetric-modulated arc therapy (VMAT) are the most preferred methods. In this study, we report a comparison study measuring the dose distribution and delivery efficiency differences between DCAT and VMAT for liver SBRT. All patients who were treated with SBRT for primary or metastatic liver tumors with a curative aim between January 2016 and December 2017 at DIRAMS were enrolled in the study. For all patients, SBRT plans were designed using the Monte Carlo (MC) algorithm in Monaco treatment planning system (version 5.1). The planning goals were set according to the RTOG 0813, RTOG 0915, and RTOG 1112 protocols. A plan comparison was made on the metrics of dose volume histogram, planning and delivery efficiency, monitor unit (MU), and dosimetric indices. PTV coverage was evaluated using the following: Dmean, D95%, D98%, D2%, D50%, Dmax, V95%, heterogeneity index (HI), and conformality index (CI). For DCAT and VMAT, respectively, the Dmean was 5942.8 ± 409.3 cGy and 5890.6 ± 438.8 cGy, D50% was 5968.8 ± 413.1 cGy and 5954.3 ± 405.2 cGy, and CI was 1.05 ± 0.05 and 1.03 ± 0.04. The D98% and V95% were 5580.0 ± 465.3 cGy and 20.4 ± 12.0 mL for DCAT, and 5596.0 ± 478.7 cGy and 20.5 ± 12.0 mL for VMAT, respectively. For normal liver, V40, V30, V20, V17, V5, Dmean, Dmax were evaluated for comparison. The V30, V20, and V10 were significantly higher in DCAT; other parameters of normal livers showed no statistically significant differences. For evaluation of intermediate dose spillage, D2cm(%) and R50% of DCAT and VMAT were 45.8 ± 7.9 and 5.6 ± 0.9 and 45.1 ± 6.7 and 5.5 ± 1.2, respectively. Planning and delivery efficiency were evaluated using MU, Calculation time, and Delivery time. DCAT had shorter Calculation time and Delivery time with smaller MU. MU was smaller in DCAT and the average difference was 300.1 MU. For liver SBRT, DCAT is an effective alternative to VMAT plans that could meet the planning goals proposed by the RTOG SBRT protocol and increases plan and delivery effectiveness, while also ignoring the interplay effect.

Added value of invasive needle techniques in mediastinal and hilar nodal staging of clinical N0-N1 non-small cell lung cancer after positron emission tomography.

Previous studies evaluating staging methods of lung cancer have focused on mediastinal disease. We explored the added value of endoscopic techniques after PET scan in the evaluation of N1 nodal stations in 276 patients with a radiologically normal mediastinum demonstrating a potential stage shift in 20% of patients.

Scores of Child-Pugh Classification Impact Overall Survival After Stereotactic Body Radiation Therapy for Primary and Metastatic Liver Tumors.

BACKGROUND: Stereotactic body radiotherapy (SBRT) delivers high-dose radiation to tumor tissues in few fractions, thereby reducing radiation damage to at-risk organs. There are more potential effects of SBRT owing to the higher biological equivalent dose delivered. Herein, we retrospectively analyzed its effectiveness and toxicity at our institution. METHODS: Data from patients with hepatocellular carcinoma (HCC; n = 10) and liver metastases (n = 10) who underwent SBRT (total dose of 30-50 Gy in 5-10 fractions) between 2013 and 2016 were analyzed. Adverse events were recorded at the end of RT, 6 months after treatment, or upon death. Overall survival (OS) was calculated according to the biological effective dose (BED α/ß = 10) and liver function (Child-Pugh [CP] classification 5 or 6 vs. 7 or 8) after SBRT, using Kaplan-Meier analyses. RESULTS: Of the 20 patients, 6 declined the CP classification score after SBRT; grade 3 adverse events were not seen in any patient. A higher OS rate was seen in patients receiving a higher BED and in those with better CP classification after SBRT. Kaplan-Meier survival analysis yielded a median OS of 401 days and 1- and 2-year OS of 45% and 15%, respectively. CONCLUSION: The higher BED was significantly associated with tumor control, and there were no differences in the tumor control rate between HCC and metastatic tumors. Changes in CP scores after SBRT also affected the survival rate. Good liver function may permit multiple rounds of SBRT.

Local control and vertebral compression fractures following stereotactic body radiotherapy for spine metastases.

PURPOSE: We aimed to retrospectively assess the incidence of vertebral compression fractures (VCF), examine clinicopathologic factors potentially associated with VCF, and evaluate treatment response in patients who received stereotactic body radiotherapy (SBRT) for spine metastases (spMets). METHODS AND MATERIALS: We identified 78 patients with 125 spMets at baseline and subsequent assessments. Patients received SBRT doses of 16 or 18 Gy. Patients with pre-existing VCF and co-existing local progression were excluded. Spine instability neoplastic score (SINS) was used for spMets categorization. Response to SBRT and VCF were assessed according to the Positron Emission tomography Response Criteria In Solid Tumors (PERCIST) and Genant scores, respectively. Kaplan-Meier analyses were used to assess local control of disease and vertebral compression fracture-free survival (FFS). RESULTS: We treated 103 cases with single spMets and 11 cases involving double spMets with SBRT. Progressive disease was reported in 3.2% and 8.2% of the cases in the first and last PET/CT reports, respectively. The distribution of treatment response in the remaining patients was: complete response in 30.6% of patients, partial response in 47.1% of patients, and stable disease in 22.3% of patients in the first PET/CT; complete response in 62.3% of patients, partial response in 16.7% of patients, and stable disease in 21% of patients at the last monitoring. Local failures were observed in 15 (12%) of cases. Median SINS was 5 (range: 1-13); majority of patients in our cohort (70.4%) were categorized as stable according to SINS, five (4%) patients had Grade 3 VCF at a median time of 16 months after SBRT (range: 2-22 months), and 60% of VCF occurred after an interval of at least 12 months after SBRT. No bisphosphonate usage was significantly associated with VCF (r = -0.204; p = 0.022). Median FFS was 21 months. Univariate analyses indicated that female gender (p < 0.001), bisphosphonate use (p = 0.005), >6 months of bisphosphonates use (p = 0.002), and the lowest vertebral body collapse score (p = 0.023) were associated with higher FFS. Female gender (p = 0.007), >6 months of bisphosphonates usage (p = 0.018), and the lowest vertebral body collapse score (p = 0.044) retained independent significance. CONCLUSIONS: This study demonstrated that spine SBRT with doses of 16-18 Gy promises good local control of disease with acceptable VCF rates. Lowest vertebral body collapse score, female gender, and >6 months of bisphosphonate use were significantly associated with longer FFS.