Recent studies have postulated that patients undergoing lung stereotactic body radiotherapy (SBRT) for ultracentral tumors have higher toxicity and mortality rates than those with central tumors. Our ...aim was to compare the outcomes after lung SBRT for central versus ultracentral tumors in our own series.
This was a retrospective review of patients with primary and metastatic lung tumors treated with SBRT from 1 September 2009 to 30 June 2015. Patients were included if they were treated with five-fraction SBRT to central or ultracentral tumors. Central tumors were defined as tumors where the closest point was within 2 cm of (but not abutting) the proximal bronchial tree, or within 2 cm of (whether abutting or not) mediastinal structures. Ultracentral tumors were defined as tumors abutting the proximal bronchial tree. The 2-year overall survival (OS), 2-year local failure (LF), and 2-year grade ≥3 toxicity rates were compared between patients with central and ultracentral tumors.
A total of 107 patients were included in this study. There were no significant differences in 2-year OS between the two groups, with 2-year OS 57.7% for central tumors, and 50.4% for ultracentral tumors (p = 0.10). There were no significant differences in 2-year LF between the two groups, with 2-year LF 3.4% for central tumors and 4.3% for ultracentral tumors (p = 0.92). There were no significant differences in 2-year grade ≥3 toxicity rate for the two groups, with 3.5% with central tumors and 8.7% with ultracentral tumors (p = 0.23).
There were no significant differences in OS, LF, or grade ≥3 toxicity between patients with central and ultracentral lung tumors. Although these results indicate that SBRT for ultracentral tumors may be safe, caution should be applied in selecting and treating these patients until the completion of large prospective trials.
•The 1- and 5-year local recurrence rates were 13.6% and 44.3, respectively.•The 2-and 5-year overall survival rates were 76.1% and 35.9%, respectively.•A biological equivalent dose of ≥120 Gy led to ...an improvement in local recurrence.•The presence of lung metastases was associated with improved local recurrence.•A larger total PTV size (≥17.5 cc) was associated with worse OS, PFS, and WSP.
In recent years, stereotactic body radiotherapy (SBRT) has emerged as an effective treatment for oligometastatic cancers. Here, we report radiation treatment parameters and clinical outcomes for patients with oligometastatic colorectal cancer (CRC) treated with SBRT using a large multi-institutional database.
Patients with extra-cranial oligometastatic CRC (≤5 lesions) treated with SBRT at six large academic cancer centers were included. The primary outcome was local recurrence while secondary outcomes included overall survival (OS) progression free survival, oligo-progression, and widespread progression. Survival outcomes were estimated using the Kaplan-Meier method. Univariable and multivariable analyses were performed to determine the relationship between patient and treatment characteristics and clinical outcomes.
We identified 235 patients with a total of 381 oligometastatic CRC lesions. The 1- and 5-year local recurrence rate was 13.6% and 44.3% respectively. The median OS was 49 months with a 2-and 5-year OS of 76.1% and 35.9%, respectively. On multivariable analysis, a BED10 of ≥120 Gy, and lung versus liver metastases were associated with a reduction in local recurrence. Larger total PTV size (≥17.5 cc) was associated with worse overall survival, progression free survival, and widespread progression.
This large multi-institutional analysis found that the use of SBRT for oligometastatic colorectal cancer resulted in favorable overall survival. However, local recurrence is higher than expected for ablative radiation treatment. An increase in BED10 should be considered if feasible and safe.
To assess the association between colorectal cancer (CRC) histology, dose, and local failure (LF) after stereotactic ablative radiation therapy (SABR) for pulmonary metastases, and to describe ...subsequent cancer progression, change of systemic therapy (CST), survival, and their association with treatment indications.
From a prospective SABR cohort, 180 pulmonary metastases in 120 patients were identified. Treatment indications were single metastasis, oligometastases, oligoprogression, and dominant areas of progression. Doses of 48 to 52 Gy/4 to 5 fractions were delivered. Since 2010 the dose for peripheral CRC metastases was increased to 60 Gy/4 fractions. Cumulative incidence function (CIF) was used to report LF, progression probability, and CST. The Kaplan-Meier method estimated overall survival (OS). Univariate and multivariable analyses to assess variable associations were conducted.
Median follow-up was 22 months (interquartile range, 14-33 months). At 24 months, the CIF of LF was 23.6% (95% confidence interval CI 15.1%-33.3%) and 8.3% (95% CI 2.6%-18.6%), respectively, for CRC and non-CRC metastases (P<.001). This association remained significant after adjusting for confounders (subdistribution hazard ratio SHR 13.6, 95% CI 4.2-44.1, P<.001). Among CRC metastases, 56 and 45 received <60 Gy and 60 Gy, respectively. Delivering 60 Gy was independently associated with a lower hazard of LF (SHR 0.271, 95% CI 0.078-0.940, P=.040). At 12 months the CIF of progression was 41.67% (95% CI 21.69%-60.56%), 42.51% (95% CI 29.09%-55.29%), 62.96% (95% CI 41.25%-78.53%), and 78.57% (95% CI 42.20%-93.48%), respectively, for patients treated for single metastasis, oligometastases, oligoprogression, and dominant area of progression (P<.001). A CST was observed, respectively, in 4 (17%), 17 (31%), 12 (44%), and 10 (71%) patients with a median time of 13.1, 11.1, 8.4, and 8.4 months.
Colorectal cancer lung metastases are associated with a higher hazard of LF and require higher SABR doses. Outcomes for patients with oligometastases and oligoprogression treated with SABR seem favorable. Prospective clinical trials are needed to confirm these benefits.
To report local control and toxicity rates for patients treated with stereotactic body radiotherapy (SBRT) for non-spine bone metastases.
Eighty-one patients with 106 non-spine bone metastases were ...treated between 2011 and 2014 and retrospectively reviewed. Indications included: oligometastases (63%), oligoprogression (17.3%), retreatment (2.4%) or other (17.3%). Cumulative incidence function was used to assess local recurrence and fracture probability. Bivariate relationships were investigated based on selected patient, tumour and dose–volume factors.
Mean follow-up was 13 months (range, 0.25–45.6) and the median patient age was 66.4 years (range, 36–86). Most patients were male (60.5%) and the predominant histology prostate cancer (32%). Bone metastases were most commonly located in the pelvis (41.5%) and almost half sclerotic. The most common prescriptions were 30 Gy/5 (30.2%) and 35 Gy/5 (42.5%). The cumulative incidence of local recurrence at 6,18 and 24 months respectively was 4.7%, 8.3% and 13.3% with a mean time to local recurrence of 11.8 months (range, 3.9–23.4). A significant association was found between local recurrence and volume of the PTV (p = 0.02), with larger PTVs having a greater risk of local failure. Fracture was observed radiographically in the treatment volume in 9/106 (8.5%) of treated lesions and the mean time to fracture was 8.4 months (range, 0.7–32.5 months). With respect to predictors, a trend was observed for lytic lesions (p = 0.11) and female gender (p = 0.09).
The results of this study confirm that SBRT yields high rates of long-term local control for non-spine bone metastases with a low fracture risk.
A co-registered multimodality pattern analysis segmentation system (COMPASS) was developed to automatically delineate the radiation targets in head-and-neck cancer (HNC) using both (18)F-fluoro-deoxy ...glucose-positron emission tomography (PET) and computed tomography (CT) images. The performance of the COMPASS was compared with the results of existing threshold-based methods and radiation oncologist-drawn contours.
The COMPASS extracted texture features from corresponding PET and CT voxels. Using these texture features, a decision-tree-based K-nearest-neighbor classifier labeled each voxel as either "normal" or "abnormal." The COMPASS was applied to the PET/CT images of 10 HNC patients. Automated segmentation results were validated against the manual segmentations of three radiation oncologists using the volume, sensitivity, and specificity. The performance of the COMPASS was compared with three PET-based threshold methods: standard uptake value of 2.5, 50% maximal intensity, and signal/background ratio.
The tumor delineations of the COMPASS were both quantitatively and qualitatively more similar to those of the radiation oncologists than the delineations from the other methods. The specificity was 95% +/- 2%, 84% +/- 9%, 98% +/- 3%, and 96% +/- 4%, and the sensitivity was 90% +/- 12%, 93% +/- 10%, 48% +/- 20%, and 68% +/- 25% for the COMPASS, for a standard uptake value of 2.5, 50% maximal intensity, and signal/background ratio, respectively. The COMPASS distinguished HNC from adjacent normal tissues with high physiologic uptake and consistently defined tumors with large variability in (18)F-fluoro-deoxy glucose uptake, which are often problematic with the threshold-based methods.
Automated segmentation using texture analysis of PET/CT images has the potential to provide accurate delineation of HNC. This could lead to reduced interobserver variability, reduced uncertainty in target delineation, and improved treatment planning accuracy.
To investigate the role of quantitative ultrasound (QUS) radiomics to predict treatment response in patients with head and neck squamous cell carcinoma (HNSCC) treated with radical radiotherapy (RT). ...Five spectral parameters, 20 texture, and 80 texture-derivative features were extracted from the index lymph node before treatment. Response was assessed initially at 3 months with complete responders labelled as early responders (ER). Patients with residual disease were followed to classify them as either late responders (LR) or patients with persistent/progressive disease (PD). Machine learning classifiers with leave-one-out cross-validation was used for the development of a binary response-prediction radiomics model. A total of 59 patients were included in the study (22 ER, 29 LR, and 8 PD). A support vector machine (SVM) classifier led to the best performance with accuracy and area under curve (AUC) of 92% and 0.91, responsively to define the response at 3 months (ER vs. LR/PD). The 2-year recurrence-free survival for predicted-ER, LR, PD using an SVM-model was 91%, 78%, and 27%, respectively (p < 0.01). Pretreatment QUS-radiomics using texture derivatives in HNSCC can predict the response to RT with an accuracy of more than 90% with a strong influence on the survival.Clinical trial registration: clinicaltrials.gov.in identifier NCT03908684.
Purpose:
To update our experience with intensity-modulated radiotherapy (IMRT) in the treatment of nasopharyngeal carcinoma (NPC).
Methods and Materials:
Between April 1995 and October 2000, 67 ...patients underwent IMRT for NPC at the University of California-San Francisco (UCSF). There were 20 females and 47 males, with a mean age of 49 (range 17–82). The disease was Stage I in 8 (12%), Stage II in 12 (18%), Stage III in 22 (33%), and Stage IV in 25 (37%). IMRT was delivered using three different techniques: 1) manually cut partial transmission blocks, 2) computer-controlled auto-sequencing segmental multileaf collimator (SMLC), and 3) sequential tomotherapy using a dynamic multivane intensity modulating collimator (MIMiC). Fifty patients received concomitant cisplatinum and adjuvant cisplatinum and 5-FU chemotherapy according to the Intergroup 0099 trial. Twenty-six patients had fractionated high-dose-rate intracavitary brachytherapy boost and 1 patient had gamma knife radiosurgery boost after external beam radiotherapy.
The prescribed dose was 65–70 Gy to the gross tumor volume (GTV) and positive neck nodes, 60 Gy to the clinical target volume (CTV), 50–60 Gy to the clinically negative neck, and 5–7 Gy in 2 fractions for the intracavitary brachytherapy boost. Acute and late normal tissue effects were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. The local progression-free, local-regional progression-free, distant metastasis-free rates, and the overall survival were calculated using the Kaplan-Meier method.
Results:
With a median follow-up of 31 months (range 7 to 72 months), there has been one local recurrence at the primary site. One patient failed in the neck. Seventeen patients developed distant metastases; 5 of these patients have died. The 4-year estimates of local progression-free, local-regional progression-free, and distant metastases-free rates were 97%, 98%, and 66% respectively. The 4-year estimate of overall survival was 88%. The worst acute toxicity documented was as follows: Grade 1 or 2 in 51 patients, Grade 3 in 15 patients, and Grade 4 in 1 patient. The worst late toxicity was Grade 1 in 20 patients, Grade 2 in 15 patients, Grade 3 in 7 patients, and Grade 4 in 1 patient. At 3 months after IMRT, 64% of the patients had Grade 2, 28% had Grade 1, and 8% had Grade 0 xerostomia. Xerostomia decreased with time. At 24 months, only one of the 41 evaluable patients had Grade 2, 32% had Grade 1, and 66% had Grade 0 or no xerostomia. Analysis of the dose-volume histograms (DVHs) showed that the average maximum, mean, and minimum dose delivered were 79.3 Gy, 74.5 Gy, and 49.4 Gy to the GTV, and 78.9 Gy, 68.7 Gy, and 36.8 Gy to the CTV. An average of only 3% of the GTV and 3% of the CTV received less than 95% of the prescribed dose.
Conclusion:
Excellent local-regional control for NPC was achieved with IMRT. IMRT provided excellent tumor target coverage and allowed the delivery of a high dose to the target with significant sparing of the salivary glands and other nearby critical normal tissues.
Background and purpose
This study aimed to summarize the clinical outcomes of patients with metastatic melanoma who received high‐dose radiation prior to or during systemic therapy at a single ...academic institution.
Methods
We identified patients with metastatic melanoma who underwent high‐dose radiation therapy (HDRT) for extracranial metastases prior to or during systemic therapy from 2010 to 2018. Treatment indications included oligometastases, oligoprogression, and local control. Using the Kaplan‐Meier method, we plotted overall survival (OS), progression‐free survival‐1 (PFS1), and PFS2. Competing risk analysis determined the cumulative incidence of local failure (LF) and the time to start or change systemic therapy (SCST). Univariate and multivariable analyses were used to identify predictive factors.
Results
We analyzed 34 patients with 79 lesions, with a median follow‐up of 17.4 months. Sixty‐eight percent of patients received systemic therapy after the first HDRT. The median OS was 22 months, with brain metastases before HDRT being a significant predictor in multivariable analysis. The median PFS1 for first‐line HDRT was 4.1 months, and the median PFS2 was 3.9 months. Rates of LF were 10.3% at 12 months and 11.7% at 24 months. The incidence of SCST following HDRT was 59.8% at 12 months and 76.1% at 24 months, with radiation targeted at the lung associated with a lower incidence of SCST.
Conclusion
HDRT for treating metastatic lesions in melanoma demonstrated excellent local control and may play a role in delaying SCST. Additional courses of HDRT may provide cumulative benefits.
Patients with metastatic melanoma receiving high dose radiotherapy (HDRT) for oligoprogression, oligometastases or improved local control were retrospectively reviewed. The 1 year rate of local failure was 10.3%, and 1 year incidence of starting or changing systemic therapy after HDRT was 59.8%.
Stereotactic body radiotherapy (SBRT) is increasingly used to treat disease in the oligometastatic (OM) setting due to mounting evidence demonstrating its efficacy and safety. Given the low ...population representation in prospective studies, we performed a systematic review and meta-analysis of outcomes of HNC patients with extracranial OM disease treated with SBRT.
A systematic review was conducted with Cochrane, Medline, and Embase databases queried from inception to August 2022 for studies with extracranial OM HNC treated with stereotactic radiotherapy. Polymetastatic patients (>five lesions), mixed-primary cohorts failing to report HNC separately, lack of treatment to all lesions, nonquantitative endpoints, and other definitive treatments (surgery, conventional radiotherapy, and radioablation) were excluded. The meta-analysis examined the pooled effects of 12- and 24-month local control (LC) per lesion, progression-free survival (PFS), and overall survival (OS). Weighted random-effects were assessed using the DerSimonian and Laird method, with heterogeneity evaluated using the
statistic and Cochran Qtest. Forest plots were generated for each endpoint.
Fifteen studies met the inclusion criteria (639 patients, 831 lesions), with twelve eligible for quantitative synthesis with common endpoints and sufficient reporting. Fourteen studies were retrospective, with a single prospective trial. Studies were small, with a median of 32 patients (range: 6-81) and 63 lesions (range: 6-126). The OM definition varied, with a maximum of two to five metastases, mixed synchronous and metachronous lesions, and a few studies including oligoprogressive lesions. The most common site of metastasis was the lung. Radiation was delivered in 1-10 fractions (20-70 Gy). The one-year LC (LC1), reported in 12 studies, was 86.9% (95% confidence interval CI: 79.3-91.9%). LC2 was 77.9% (95% CI: 66.4-86.3%), with heterogeneity across studies. PFS was reported in five studies, with a PFS1 of 43.0% (95% CI: 35.0-51.4%) and PFS2 of 23.9% (95% CI: 17.8-31.2%), with homogeneity across studies. OS was analyzed in nine studies, demonstrating an OS1 of 80.1% (95% CI: 74.2-85.0%) and OS2 of 60.7% (95% CI: 51.3-69.4%). Treatment was well tolerated with no reported grade 4 or 5 toxicities. Grade 3 toxicity rates were uniformly below 5% when reported.
SBRT offers excellent LC and promising OS, with acceptable toxicities in OM HNC. Durable PFS remains rare, highlighting the need for effective local or systemic therapies in this population. Further investigations on concurrent and adjuvant therapies are warranted.
To evaluate the applicability of the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and University of Texas MD Anderson (MDA) Cancer Center criteria in the setting of stereotactic body ...radiation therapy (SBRT) to nonspine bone metastases.
Patients who were treated with SBRT to nonspine bone metastases were identified by retrospective chart review. An independent musculoskeletal radiologist evaluated response to treatment using computed tomography (CT) scans.
Thirty-three patients were treated to 42 nonspine bone metastases. The most common primary cancer cites were renal cell carcinoma (RCC) (33.3%), lung (24.2%), and prostate (18.2%). Bone metastases were either mainly lytic (57.1%), mainly sclerotic (28.6%), or mixed (14.3%). When lytic and sclerotic lesions were evaluated according to RECIST 1.1, local control (LC) was 83%, 85%, 88%, and 80% for those with CT imaging between months 1 to 3, 4 to 6, 7 to 9, and 10 to 12, respectively. When evaluated by the MDA criteria by density, LC within each time period was slightly greater. Overall LC decreased considerably when evaluated by MDA in terms of size.
Consensus definitions of response are required as they have implications on clinical trials and disease management. Without consistent response criteria, outcomes from clinical trials cannot be compared and treatment efficacy remains undetermined.
PDF
