The objective of this study was to assess the cosmesis and toxicities in patients with early-stage breast carcinoma who received treatment with accelerated partial breast irradiation (APBI) using ...interstitial brachytherapy.
From April 1993 to December 2001, 199 patients with Stage I-II breast carcinoma received breast-conserving therapy with APBI to the tumor bed alone through a low-dose-rate (LDR) or high-dose-rate (HDR) implant. A template guide was used. The LDR dose was 50 Gray (Gy) over 96 hours; the outpatient HDR implant delivered 32 Gy in 8-Gy or 34 Gy in 10-Gy twice-daily fractions. Cosmesis (Harvard criteria) and toxicities (Radiation Therapy Oncology Group guidelines) were assessed at < or = 6 months, 2 years, and 5 years.
The median follow up was 6.4 years. Breast pain, edema, erythema, and hyperpigmentation all diminished over time. Breast fibrosis and hypopigmentation increased until the 2-year mark and then stabilized. Fat necrosis and telangiectasia increased over time, with a fat necrosis rate of 11% at 5 years. Nearly all telangiectasias (34% at 5 yrs) were Grade 1 (< 2 mm). The remaining toxicities were Grade 1 at all follow-up intervals. Infections (11%) occurred predominantly within the first month after treatment. Good-to-excellent cosmetic outcomes were noted in 95-99% of patients over time; cosmetic results stabilized at 2 years with excellent results increased out to 5 years.
APBI with interstitial brachytherapy resulted in mild chronic toxicities, the majority of which diminished or reached a plateau over time. Long-term cosmesis was good to excellent in 95-99% of patients and stabilized at 2 years.
The standard-of-care therapy for extensive-stage SCLC has recently changed with the results of two large randomized trials revealing improved survival with the addition of immunotherapy to first-line ...platinum or etoposide chemotherapy. This has led to a lack of clarity around the role of consolidative thoracic radiation and prophylactic cranial irradiation in the setting of chemoimmunotherapy.
The American Radium Society Appropriate Use Criteria are evidence-based guidelines for specific clinical conditions that are reviewed by a multidisciplinary expert panel. The guidelines include a review and analysis of current evidence with the application of consensus methodology (modified Delphi) to rate the appropriateness of treatments recommended by the panel for extensive-stage SCLC.
Current evidence supports either prophylactic cranial irradiation or surveillance with magnetic resonance imaging every 3 months for patients without evidence of brain metastases. Patients with brain metastases should receive whole-brain radiation with a recommended dose of 30 Gy in 10 fractions. Consolidative thoracic radiation can be considered in selected cases with the recommended dose ranging from 30 to 54 Gy; this recommendation was driven by expert opinion owing to the limited strength of evidence, as clinical trials addressing this question remain ongoing.
Radiation therapy remains an integral component in the treatment paradigm for ES-SCLC.
Purpose: To evaluate the heart and lung sparing effects of moderate deep inspiration breath hold (mDIBH) achieved using an active breathing control (ABC) device, compared with free breathing (FB) ...during treatment with deep tangents fields (DT) for locoregional (LR) irradiation of breast cancer patients, including the internal mammary (IM) nodes (IMNs). To compare the DT-mDIBH technique to other standard techniques and to evaluate the dosimetric effect of intensity-modulated radiation therapy (IMRT).
Methods and Materials: Fifteen patients (9 left-sided and 6 right-sided lesions) with Stages 0–III breast cancer underwent standard FB and ABC computed tomographic (CT) scans in the treatment position. A dosimetric planning study was performed. In FB, the 9 left-sided patients were planned with a 5-field technique where electron fields covering the IM region were matched to shallow tangents using wedges (South West Oncology Group SWOG protocol S9927 technique A). This method was compared with a 3-field DT technique covering the breast and the IMNs (SWOG S9927 technique B). Compensation with IMRT was then compared with wedges for each technique. For the 15 total patients, dosimetric planning using DT with IMRT was then reoptimized on the mDIBH CT data set for comparison. Dose-volume histograms for the clinical target volume (CTV) (including the IMNs), planning target volume (PTV), ipsilateral and contralateral breast, and organs at risk (OAR) were analyzed. In addition, normal tissue complication probabilities (NTCP) for lung and heart, mean lung doses, and the number of monitor units (MUs) for a 1.8 Gy fraction were compared.
Results: For the 9 left-sided patients, the mean percentage of heart receiving more than 30 Gy (heart V30) was lower with the 5-field wedged technique than with the DT wedged technique (6.8% and 19.1%, respectively,
p < 0.004). For the DT technique, the replacement of wedges with IMRT slightly diminished the mean heart V30 to 16.3% (
p < 0.51). The introduction of mDIBH to the DT-IMRT technique reduced the heart V30 by 81% to a mean of 3.1% (
p < 0.0004). Compared with 5-field IMRT, DT-IMRT with mDIBH reduced the heart V30 for 6 of the 9 patients, entirely avoiding heart irradiation in 2 of these 6 patients. For DT-IMRT, mDIBH reduced the mean lung dose and NTCP to levels obtained with the 5-field IMRT technique. For the 15 patients planned with DT-IMRT in FB, the use of mDIBH reduced the mean percentage of both lungs receiving more than 20 Gy from 20.4% to 15.2% (
p < 0.00007). With DT-IMRT, more than 5% of the contralateral breast received more than 10 Gy for 6 of the 9 left-sided patients in FB, 3 of those 9 patients in mDIBH, and only 1 of those 9 patients planned with 5 fields. The mean % of the PTV receiving more than 55 Gy (110% of the prescribed dose) was 36.4% for 5-field wedges, 33.4% for 5-field IMRT, 28.7% for DT-wedges, 12.5% for DT-IMRT, and 18.4% for DT-IMRT mDIBH. The CTV remained covered by the 95% isodose in all the DT plans but one (99.1% of the volume covered). DT-wedges required more MUs than DT-IMRT (mean of 645 and 416, respectively,
p < 0.00004).
Conclusion: mDIBH significantly reduces heart and lung doses when DT are used for LR breast irradiation including the IMNs. Compared with shallow tangents matched with electrons, DT with mDIBH reduces the heart dose (in most patients) and results in comparable lung toxicity parameters, but may increase the dose to the contralateral breast. IMRT improves dose homogeneity, slightly reduces the dose to the heart, and diminishes the number of MUs required.
Treatment for inoperable stage II to III non-small cell lung cancer (NSCLC) involves chemo-radiotherapy (CRT). However, some patients transition to hospice or die early during their treatment course. ...We present a model to prognosticate early poor outcomes in NSCLC patients treated with curative-intent CRT.
Across a statewide consortium, data was prospectively collected on stage II to III NSCLC patients who received CRT between 2012 and 2019. Early poor outcomes included hospice enrollment or death within 3 months of completing CRT. Logistic regression models were used to assess predictors in prognostic models. LASSO regression with multiple imputation were used to build a final multivariate model, accounting for missing covariates.
Of the 2267 included patients, 128 experienced early poor outcomes. Mean age was 71 years and 59% received concurrent chemotherapy. The best predictive model, created parsimoniously from statistically significant univariate predictors, included age, ECOG, planning target volume (PTV), mean heart dose, pretreatment lack of energy, and cough. The estimated area under the ROC curve for this multivariable model was 0.71, with a negative predictive value of 95%, specificity of 97%, positive predictive value of 23%, and sensitivity of 16% at a predicted risk threshold of 20%.
This multivariate model identified a combination of clinical variables and patient reported factors that may identify individuals with inoperable NSCLC undergoing curative intent chemo-radiotherapy who are at higher risk for early poor outcomes.
Stage II to III non-small-cell lung cancer(NSCLC) treatment involves chemo-radiotherapy(CRT). We present a model-including age, ECOG, planning target volume, heart dose, lack of energy, and cough-prognosticating early poor outcomes. The area under the ROC curve was 0.71, with NPV 95%, specificity 97%, PPV 23%, sensitivity 16% at a risk threshold of 20%. This multivariate model may identify patients at risk for early poor outcomes.
F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging is now considered the most accurate clinical staging study for non–small-cell lung cancer (NSCLC) and is also important in the ...staging of multiple other malignancies. Gross tumor volume (GTV) definition for radiotherapy, however, is typically based entirely on computed tomographic data. We performed a series of phantom studies to determine an accurate and uniformly applicable method for defining a GTV with FDG-PET.
A model-based method was tested by a phantom study to determine a threshold, or unique cutoff of standardized uptake value based on body weight (standardized uptake value SUV) for FDG-PET based GTV definition. The degree to which mean target SUV, background FDG concentration, and target volume influenced that GTV definition were evaluated. A phantom was constructed consisting of a 9.0-L cylindrical tank. Glass spheres with volumes ranging from 12.2 to 291.0 cc were suspended within the tank, with a minimum separation of 4 cm between the edges of the spheres. The sphere volumes were selected based on the range of NSCLC patient tumor volumes seen in our clinic. The tank and spheres were filled with a variety of known concentrations of FDG in several experiments and then scanned using a General Electric Advance PET scanner. In the initial experiment, six spheres with identical volumes were filled with varying concentrations of FDG (mean SUV = 1.85 ∼ 9.68) and suspended within a background bath of FDG at a similar concentration to that used in clinical practice (0.144 μCi/mL). The second experiment was identical to the first, but was performed at 0.144 and 0.036 μCi/mL background concentrations to determine the effect of background FDG concentration on sphere definition. In the third experiment, six spheres with volumes of 12.2 to 291.0 cc were filled with equal concentrations of FDG and suspended in a standard background FDG concentration of 0.144 μCi/mL. Sphere images in each experiment were auto-contoured (simulating a GTV) using the threshold SUV that yielded a volume matching that of the known sphere volume. A regressive function was constructed to represent the relationship between the threshold SUV and the mean target SUV. This function was then applied to define the GTV of 15 NSCLC patients. The GTV volumes were compared to those determined by a fixed image intensity threshold proposed by other investigators.
There was a strong linear relationship between the threshold SUV and the mean target SUV. The linear regressive function derived was: threshold SUV = 0.307 × (mean target SUV) + 0.588. The background concentration and target volume indirectly affect the threshold SUV by way of their influence on the mean target SUV. We applied the linear regressive function, as well as a fixed image intensity threshold (42% of maximum intensity) to the sphere phantoms and 15 patients with NSCLC. The results indicated that a much smaller deviation occurred when the threshold SUV regressive function was utilized to estimate the phantom volume as compared to the fixed image intensity threshold. The average absolute difference between the two methods was 21% with respect to the true phantom volume. The deviation became even more pronounced when applied to true patient GTV volumes, with a mean difference between the two methods of 67%. This was largely due to a greater degree of heterogeneity in the SUV of tumors over phantoms.
An FDG-PET-based GTV can be systematically defined using a threshold SUV according to the regressive function described above. The threshold SUV for defining the target is strongly dependent on the mean target SUV of the target, and can be uniquely determined through the proposed iteration process.
Combined modality therapy with concurrent chemotherapy and radiation has long been the standard of care for limited-stage SCLC (LS-SCLC). However, there is controversy over best combined modality ...practices for LS-SCLC. To address these controversies, the American Radium Society (ARS) Thoracic Appropriate Use Criteria (AUC) Committee have developed updated consensus guidelines for the treatment of LS-SCLC.
The ARS AUC are evidence-based guidelines for specific clinical conditions that are reviewed by a multidisciplinary expert panel. The guidelines include a review and analysis of current evidence with application of consensus methodology (modified Delphi) to rate the appropriateness of treatments recommended by the panel for LS-SCLC. Agreement or consensus was defined as less than or equal to 3 rating points from the panel median. The consensus ratings and recommendations were then vetted by the ARS Executive Committee and subject to public comment before finalization.
The ARS Thoracic AUC committee developed multiple consensus recommendations for LS-SCLC. There was strong consensus that patients with unresectable LS-SCLC should receive concurrent chemotherapy with radiation delivered either once or twice daily. For medically inoperable T1-T2N0 LS-SCLC, either concurrent chemoradiation or stereotactic body radiation followed by adjuvant chemotherapy is a reasonable treatment option. The panel continues to recommend whole-brain prophylactic cranial irradiation after response to chemoradiation for LS-SCLC. There was panel agreement that prophylactic cranial irradiation with hippocampal avoidance and programmed cell death protein-1/programmed death-ligand 1–directed immune therapy should not be routinely administered outside the context of clinical trials at this time.
The ARS Thoracic AUC Committee provide consensus recommendations for LS-SCLC that aim to provide a groundwork for multidisciplinary care and clinical trials.
Abstract Purpose To clarify the risk of developing second primary cancers (SPCs) after radiotherapy (RT) versus prostatectomy for localized prostate cancer (PCa) in the modern era. Methods The RT ...cohort consisted of 2120 patients matched on a 1:1 basis with surgical patients according to age and follow-up time. RT techniques consisted of conventional or two-dimensional RT (2DRT, 36%), three-dimensional conformal RT and/or intensity modulated RT (3DCRT/IMRT, 29%), brachytherapy (BT, 16%), and a combination of 2DRT and BT (BT boost, 19%). Results The overall SPC risk was not significantly different between the matched-pair (HR 1.14, 95% CI 0.94–1.39), but the risk became significant >5 years or >10 years after RT (HR 1.86, 95% CI 1.36–2.55; HR 4.94, 95% CI 2.18–11.2, respectively). The most significant sites of increased risk were bladder, lymphoproliferative, and sarcoma. Of the different RT techniques, only 2DRT was associated with a significantly higher risk (HR 1.76, 95% CI 1.32–2.35), but not BT boost (HR 0.83, 95% CI 0.50–1.38), 3DCRT/IMRT (HR 0.81, 95% CI 0.55–1.21), or BT (HR 0.53, 95% CI 0.28–1.01). Conclusions Radiation-related SPC risk varies depending on the RT technique and may be reduced by using BT, BT boost, or 3DCRT/IMRT.
Radiation therapy (RT) is the standard alternative curative treatment option for medically inoperable early stage non-small-cell lung cancer (NSCLC). Recently, stereotactic body radiotherapy (SBRT) ...has shown substantial promise to improve local control rates as compared with conventional fractionated RT external beam RT (EBRT). We compare treatment outcomes and costs between SBRT and EBRT in this patient population.
A total of 86 patients with Stage I (Tl-2 N0) NSCLC were treated with either EBRT (n=41) or SBRT (n=45) between January 2002 and April 2008. EBRT patients were treated to a median dose of 70 Gy with 3-dimensional conformal RT (n=39) or intensity-modulated radiation therapy (n=2). SBRT was delivered in 4 or 5 fractions to 48 (Tl, n=44) or 60 (T2, n=1) Gy. The actual cost was calculated using 2010 Medicare hospital-based Ambulatory Payment Classification and hospital-based physician fee screen reimbursement rates for both the technical and professional components.
On the basis of a median number of fractions for this patient population, SBRT was significantly less expensive ($13,639 EBRT vs. $10,616 SBRT, P < 0.01). Survival analysis demonstrated superior 36-month overall survival using SBRT, 71% versus 42% for EBRT (P < 0.05). SBRT also reduced local failure by nearly 3 times compared with EBRT (12% vs. 34%, P=0.10).
In this study of Stage I NSCLC patients, SBRT was found to be less expensive than standard fractionated EBRT, with the cost savings highly dependent on the number of SBRT fractions and EBRT technique (3-dimensional conformal RT vs. intensity-modulated radiation therapy). SBRT was also associated with superior local control and overall survival.
To identify factors predictive for chronic urinary toxicity secondary to high-dose adaptive three-dimensional conformal radiation.
From 1999 to 2002, 331 consecutive patients with clinical Stage ...II-III prostate cancer were prospectively treated (median dose, 75.6 Gy). The bladder was contoured, and the bladder wall was defined as the outer 3 mm of the bladder solid volume. Toxicity was quantified according to the National Cancer Institute Common Toxicity Criteria 2.0. Median follow-up was 1.6 years.
The 3-year rates of Grade > or =2 and Grade 3 chronic urinary toxicity were 17.0% and 3.6%, respectively. Prostate volume, confidence-limited patient-specific planning target volume, bladder wall volume, and acute urinary toxicity were all found to be accurate predictors for chronic urinary toxicity. The volume of bladder wall receiving > or =30 Gy (V30) and > or =82 Gy (V82), along with prostate volume, were all clinically useful predictors of Grade > or =2 and Grade 3 chronic urinary toxicity and chronic urinary retention. Both Grade > or =2 (p = 0.001) and Grade 3 (p = 0.03) acute urinary toxicity were predictive for the development of Grade > or =2 (p = 0.001, p = 0.03) and Grade 3 (p = 0.05, p < 0.001) chronic urinary toxicity. On Cox multivariate analysis the development of acute toxicity was independently predictive for the development of both Grade > or =2 and Grade 3 chronic urinary toxicity.
Acute urinary toxicity and bladder wall dose-volume endpoints are strong predictors for the development of subsequent chronic urinary toxicity. Our recommendation is to attempt to limit the bladder wall V30 to <30 cm(3) and the V82 to <7 cm(3) when possible. If bladder wall information is not available, bladder solid V30 and V82 may be used.
We present our initial clinical experience using moderate deep-inspiration breath hold (mDIBH) with an active breathing control (ABC) device to reduce heart dose in the treatment of patients with ...early-stage, left-sided breast cancer using external beam radiation therapy (EBRT) limited to the whole breast.
Between February and August 2002, 5 patients with Stages I/II left-sided breast cancer received EBRT limited to the whole breast using an ABC device. After standard virtual simulation, patients with >2% of the heart receiving >30 Gy in free breathing were selected. All patients underwent a training session with the ABC apparatus to determine their ability to comfortably maintain mDIBH at 75% of the maximum inspiration capacity. Three patients received 45 Gy to the whole breast in 25 fractions, and 2 patients received 50.4 Gy in 28 fractions. For each of the medial and lateral tangential beams, radiation was delivered during 2 or 3 breath hold durations that ranged from 18 to 26 s. “Step-and-shoot” intensity modulation was employed to achieve uniform dose distribution. Open beam segments were purposely delivered over 2 breath hold sessions and captured on electronic portal images to allow intra- and interfraction setup error analysis. All electronic portal images of the tangential beams were analyzed off-line using an in-house treatment verification tool to assess the anteroposterior, craniocaudal, and rotational uncertainties. Corrections were applied if necessary.
A comparison of treatment plans performed on breath-hold and free-breathing CTs showed that ABC treatments achieved a mean absolute reduction of 3.6% in heart volume receiving 30 Gy (heart
V
30) and 1.5% in the heart normal tissue complication probability. A total of 134 ABC treatment sessions were performed in the 5 patients. The average number of breath holds required per beam direction was 2.5 (4–6 per treatment) with a median duration of 22 s per breath hold (range: 10–26 s). Patients tolerated mDIBH well. The median treatment time was 18.2 min (range: 13–32 min), which was progressively shortened with increasing experience. A total of 509 portal images were analyzed. Combining measurements for all patients, the interfraction setup errors (1 SD) in the lateral and craniocaudal directions and in rotation were 2.4 mm, 3.2 mm, and 1°, respectively, for the medial beam and 2.3 mm, 3.1 mm, and 1°, respectively, for the lateral beam. For all patients, the intrafraction setup errors were about 1 mm and always less than 2 mm (1 SD).
Reduction in heart
V
30 can be achieved in patients with left-sided breast cancer using mDIBH assisted with an ABC device. With increasing experience, ABC treatments were streamlined and could be performed within a 15-min treatment slot. Our results suggest that mDIBH using an ABC device may provide one of the most promising methods of improving the efficacy of EBRT in patients with left-sided breast cancer, particularly when wide tangential beams are employed.
Breast cancer; Breath hold; Radiation therapy; Intensity modulated radiation therapy
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