Summary Background Since the introduction of breast-conserving treatment, various radiation doses after lumpectomy have been used. In a phase 3 randomised controlled trial, we investigated the effect ...of a radiation boost of 16 Gy on overall survival, local control, and fibrosis for patients with stage I and II breast cancer who underwent breast-conserving treatment compared with patients who received no boost. Here, we present the 20-year follow-up results. Methods Patients with microscopically complete excision for invasive disease followed by whole-breast irradiation of 50 Gy in 5 weeks were centrally randomised (1:1) with a minimisation algorithm to receive 16 Gy boost or no boost, with minimisation for age, menopausal status, presence of extensive ductal carcinoma in situ, clinical tumour size, nodal status, and institution. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was overall survival in the intention-to-treat population. The trial is registered with ClinicalTrials.gov , number NCT02295033. Findings Between May 24, 1989, and June 25, 1996, 2657 patients were randomly assigned to receive no radiation boost and 2661 patients randomly assigned to receive a radiation boost. Median follow-up was 17·2 years (IQR 13·0–19·0). 20-year overall survival was 59·7% (99% CI 56·3–63·0) in the boost group versus 61·1% (57·6–64·3) in the no boost group, hazard ratio (HR) 1·05 (99% CI 0·92–1·19, p=0·323). Ipsilateral breast tumour recurrence was the first treatment failure for 354 patients (13%) in the no boost group versus 237 patients (9%) in the boost group, HR 0·65 (99% CI 0·52–0·81, p<0·0001). The 20-year cumulative incidence of ipsilatelal breast tumour recurrence was 16·4% (99% CI 14·1–18·8) in the no boost group versus 12·0% (9·8–14·4) in the boost group. Mastectomies as first salvage treatment for ipsilateral breast tumour recurrence occurred in 279 (79%) of 354 patients in the no boost group versus 178 (75%) of 237 in the boost group. The cumulative incidence of severe fibrosis at 20 years was 1·8% (99% CI 1·1–2·5) in the no boost group versus 5·2% (99% CI 3·9–6·4) in the boost group (p<0·0001). Interpretation A radiation boost after whole-breast irradiation has no effect on long-term overall survival, but can improve local control, with the largest absolute benefit in young patients, although it increases the risk of moderate to severe fibrosis. The extra radiation dose can be avoided in most patients older than age 60 years. Funding Fonds Cancer, Belgium.
Our recently developed prone crawl position (PCP) for radiotherapy of breast cancer patients with lymphatic involvement showed promising preliminary data and it is being optimized for clinical use. ...An important aspect in this process is making new, position specific delineation guidelines to ensure delineation (for treatment planning) is uniform across different centers. The existing ESTRO and PROCAB guidelines for supine position (SP) were adapted for PCP. Nine volunteers were MRI scanned in both SP and PCP. Lymph node regions were delineated in SP using the existing ESTRO and PROCAB guidelines and were then translated to PCP, based on the observed changes in reference structure position. Nine PCP patient CT scans were used to verify if the new reference structures were consistently identified and easily applicable on different patient CT scans. Based on these data, a team of specialists in anatomy, CT- and MRI radiology and radiation oncology postulated the final guidelines. By taking the ESTRO and PROCAB guidelines for SP into account and by using a relatively big number of datasets, these new PCP specific guidelines incorporate anatomical variability between patients. The guidelines are easily and consistently applicable, even for people with limited previous experience with delineations in PCP.
After breast-conserving radiation therapy most patients experience acute skin toxicity to some degree. This may impair patients' quality of life, cause pain and discomfort. In this study, we ...investigated treatment and patient-related factors, including genetic polymorphisms, that can modify the risk for severe radiation-induced skin toxicity in breast cancer patients.
We studied 377 patients treated at Ghent University Hospital and at ST.-Elisabeth Clinic and Maternity in Namur, with adjuvant intensity modulated radiotherapy (IMRT) after breast-conserving surgery for breast cancer. Women were treated in a prone or supine position with normofractionated (25 × 2 Gy) or hypofractionated (15 × 2.67 Gy) IMRT alone or in combination with other adjuvant therapies. Patient- and treatment-related factors and genetic markers in regulatory regions of radioresponsive genes and in LIG3, MLH1 and XRCC3 genes were considered as variables. Acute dermatitis was scored using the CTCAEv3.0 scoring system. Desquamation was scored separately on a 3-point scale (0-none, 1-dry, 2-moist).
Two-hundred and twenty patients (58%) developed G2+ dermatitis whereas moist desquamation occurred in 56 patients (15%). Normofractionation (both p < 0.001), high body mass index (BMI) (p = 0.003 and p < 0.001), bra cup size ≥ D (p = 0.001 and p = 0.043) and concurrent hormone therapy (p = 0.001 and p = 0.037) were significantly associated with occurrence of acute dermatitis and moist desquamation, respectively. Additional factors associated with an increased risk of acute dermatitis were the genetic variation in MLH1 rs1800734 (p=0.008), smoking during RT (p = 0.010) and supine IMRT (p = 0.004). Patients receiving trastuzumab showed decreased risk of acute dermatitis (p < 0.001).
The normofractionation schedule, supine IMRT, concomitant hormone treatment and patient related factors (high BMI, large breast, smoking during treatment and the genetic variation in MLH1 rs1800734) were associated with increased acute skin toxicity in patients receiving radiation therapy after breast-conserving surgery. Trastuzumab seemed to be protective.
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.
Interstitial lung disease (ILD) is associated with a higher lung cancer (LC) risk and may impact cancer's clinical characteristics, treatment strategies, and outcomes. This impact's extent is ...unclear, particularly in Caucasians.
In this retrospective observational study, we reviewed the files of all LC patients diagnosed in a 38-month period. Expert radiologists reviewed the computed tomography scans performed at diagnosis. Patients with LC and ILD (
= 29, 7%) were compared to those without ILD (
= 363, 93%) for population and cancer characteristics, treatments, and clinical outcomes.
Patients with LC and ILD were older (73 ± 8 vs. 65 ± 11 years;
< 0.001). There was no significant difference in LC histology, localization, stage, or treatment modalities. The respiratory complication rate after cancer treatment was significantly higher in the ILD group (39% vs. 6%;
< 0.01). Overall survival rates were similar at 12 (52% vs. 59%;
= 0.48) and 24 months (41% vs. 45%;
= 0.64) but poorer in the ILD group at 36 months, although not statistically significant (9% vs. 39%;
= 0.06). The ILD group had a higher probability of death (hazard ratio (HR) = 1.49 0.96;2.27), but this was not statistically significant (
= 0.06). In a Cox regression model, patients with ILD treated surgically had a significantly higher mortality risk (HR = 2.37 1.1;5.09;
= 0.03).
Patients with combined LC and ILD have worse clinical outcomes even when similar treatment modalities are offered.
To evaluate the outcome of patients treated with stereotactic ablative body radiotherapy (SABR) with curative intent for stage I non-small cell lung cancer (NSCLC) with regard to local, regional and ...distant tumor control, disease-free survival (DFS), overall survival (OS) and toxicity.
Data of 300 patients treated with SABR for NSCLC cancer for the period of November 2007 to June 2016 were retrospectively analyzed. Of which, 189 patients had single primary lung lesion and were included in the study. The prescribed dose for the tumor was 48 Gy, given in 12 Gy × 4 fractions for all patients. In 2010, an improved protocol was established in advanced technology for the planning CT, dose calculation and imaging. Cumulative incidence function (CIF) of local, regional, distant or any recurrences were computed using competing risk analysis with death as a competing event. Survivals (DFS and OS) were estimated using the Kaplan-Meier method and Cox proportional regression was used for comparisons. Toxicities were graded according to the common terminology criteria for adverse events version 4.0 (CTCAE v.4).
Diagnosis was histologically confirmed in 42% of the patients (N = 80). At 1, 2 and 4 years, the cumulative incidence function (CIF) of local relapses were 8% 4-13%, 15% 10-21% and 18% 12-25%, the CIF of regional relapses were 4% 2-8%, 10% 6-16% and 12% 8-19%, the CIF of distant relapses were 9% 5-14%, 15% 11-22% and 20% 15-28% and the CIF of any relapses were 14% 10-20%, 28% 22-36%, 34% 27-43%, respectively. After 1, 2 and 4 years, the OS rates were 83% 95% CI: 78-89% (N = 128), 65% 95% CI: 57-73% (N = 78) and 37% 95% CI: 29-47% (N = 53), respectively. The median survival time was 37 months. The DFS after 1, 2 and 4 years reached 75% 95% CI: 68-81% (N = 114), 49% 95% CI: 42-58% (N = 60) and 31% 95% CI: 24-41% (N = 41), respectively. No grade 4 or 5 toxicity was observed.
We observed a long-term local control and survival after SABR for peripheral stage I NSCLC in this large series of patients with the expected low toxicity.
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
Purpose: We present a novel three-dimensional conformal radiation therapy (3D-CRT) technique to treat the lumpectomy cavity, plus a 1.5-cm margin, in patients with early-stage breast cancer and study ...its clinical feasibility.
Methods and Materials: A 3D-CRT technique for partial-breast irradiation was developed using archived CT scans from 7 patients who underwent an active breathing control study. The clinical feasibility of this technique was then assessed in 9 patients who were prospectively enrolled on an Investigational Review Board-approved protocol of partial-breast irradiation. The prescribed dose was 34 Gy in 5 patients and 38.5 Gy in 4 patients, delivered in 10 fractions twice daily over 5 consecutive days. The impact of both breathing motion and patient setup uncertainty on clinical target volume (CTV) coverage was studied, and an appropriate CTV-to-PTV (planning target volume) margin was calculated.
Results: By adding a CTV-to-PTV “breathing-only” margin of 5 mm, 98%–100% of the CTV remained covered by the 95% isodose surface at the extremes of normal inhalation and normal exhalation. The “total” CTV-to-PTV margin employed to accommodate organ motion and setup error (10 mm) was found to be sufficient to accommodate the observed uncertainty in the delivery precision. Patient tolerance was excellent, and acute toxicity was minimal. No skin changes were noted during treatment, and at the initial 4–8-week follow-up visit, only mild localized hyperpigmentation and/or erythema was observed. No instances of symptomatic radiation pneumonitis have occurred.
Conclusions: Accelerated partial-breast irradiation using 3D-CRT is technically feasible, and acute toxicity to date has been minimal. A CTV-to-PTV margin of 10 mm seems to provide coverage for most patients. However, more patients and additional studies will be needed to validate the accuracy of this margin, and longer follow-up will be needed to assess acute and chronic toxicity, tumor control, and cosmetic results.
The active breathing control (ABC) apparatus was used to quantify the effect of breathing motion on whole breast radiotherapy (RT) with standard wedges and intensity-modulated RT (IMRT).
Ten patients ...with early-stage breast cancer underwent routine free-breathing (FB) CT simulations for whole breast RT. An ABC apparatus was used to obtain two additional CT scans with the breath held at the end of normal inhalation and normal exhalation. The FB scan was used to develop both a standard treatment plan using wedged coplanar tangents and an IMRT plan using multiple static multileaf collimator segments. To simulate breathing, each plan was copied and applied to the normal inhalation and normal exhalation CT scans.
The medial field border (defined by a radiopaque catheter) for the normal inhalation and normal exhalation scans moved an average of 0.6 cm anteriorly and 0.3 cm posteriorly compared with the FB position, respectively. The corresponding movement of the lateral field border was an average of 0.4 cm anteriorly and 0.2 cm posteriorly compared with the FB position. For both the wedged and the IMRT techniques, the dose delivered to breast tissue, biopsy cavity, and ipsilateral lung was similar for each of the three CT scan positions. However, the internal mammary node dose varied significantly with breathing.
The dose delivered to breast using standard wedges or step-and-shoot IMRT is relatively insensitive to the effects of breast motion during normal breathing. However, an appreciable portion of the internal mammary nodes are irradiated during normal inhalation, contributing to the uncertainty in the analysis of the efficacy of internal mammary nodal RT in breast treatment.
In Regard to Vaidya et al Meattini, Icro; Boersma, Liesbeth; Livi, Lorenzo ...
International journal of radiation oncology, biology, physics,
08/2015, Volume:
92, Issue:
5
Journal Article
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