Medial Supraclavicular Lymph Node Research Articles

The association of internal mammary and medial supraclavicular lymph node radiation technique with clinical outcomes: Results from the EORTC 22922/10925 randomised trial

Background and purposeThe multicentre EORTC 22922/10925 trial (ClinicalTrials.gov, NCT00002851) was conducted between 1996 and 2004. The trial evaluated the effect of irradiation of the internal mammary and medial supraclavicular lymph node chains (IM-MS) vs no further radiation therapy (RT) on survival and cause of death in breast cancer stage I-III patients. At 15.7 years of median follow-up, a significant reduction of breast cancer specific mortality (BCSM) and any recurrence, not translating in improved overall survival (OS), and low absolute rates of side effects were found. The aim of the current analysis was to evaluate the association of RT techniques of IM-MS lymph node irradiation with long-term outcomes. Patients and methodsThree RT techniques were used for IM-MS: a standard technique using a fixed set-up combining photon/electron beams to the IM and tangential fields to the breast or chest wall vs a standard-modified technique with minor adaptation for beam settings vs a more individualised technique based on individual localisation of the IM. Techniques used were fixed per institution over the duration of the trial. We performed an exploratory and descriptive analysis of the outcomes after 15 years follow-up for the three RT techniques. ResultsBetween July 1996 and January 2004, 46 radiation oncology departments from 13 countries accrued 4004 patients. Median follow-up was 15.7 years. The number of patients treated by each technique was 2440 (61%) by standard vs 635 (16%) by standard-modified vs 929 (23%) patients by individualised technique. The absolute improvements of oncological outcomes in terms of disease-free survival (DFS), OS and BCSM with IM-MS RT compared to no IM-MS RT were 6.8%, 4.9% and −5.8% for the individualised technique, vs 1.6%, 2.9% and −4.3% for modified standard and −1.4%, 1.1% and −3% for standard technique, respectively. The increase in 15-year rates of side effects due to IM-MS RT, both scored longitudinally and cross-sectionally, were similar among the techniques. ConclusionEven though a straightforward comparison by technique is not possible because of variations in baseline characteristics between institutions, our findings suggest that the use of more individualised RT techniques is associated with higher rates of oncological improvements without increased risks for late side effects.

Pattern of Clavicular Lymph Nodes Metastases and its Implication in Clinical Target Volume Delineation for Patients with Breast Cancer

To explore the pattern of clavicular lymph nodes metastases and provide implications for individualized clinical target volume delineation on breast cancer. We retrospectively analyzed 91 patients diagnosed as breast cancer accompanied by clavicular lymph nodes metastases between January 2015 and July 2017 in our institute. According to Breast Cancer Atlas for Radiation Therapy Planning in Radiation Therapy Oncology Group (RTOG) guideline, the clavicular lymph nodes were divided into ipsilateral medial supraclavicular lymph nodes (IMSC-LNs), ipsilateral lateral supraclavicular lymph nodes (ILSC-LNs), ipsilateral infraclavicular lymph nodes (IIC-LNs), ≥ 2 groups metastases in ipsilateral clavicular lymph nodes (TMMIC-LNs) and contralateral supraclavicular lymph nodes (CSC-LNs). Age, menopausal status, tumor location, pathologic characteristics, and immunohistochemical type were studied to identify prognostic factors associated with the prevalence of clavicular lymph node metastases. Statistical analysis was conducted using statistical software. Of the 91 patients in this study, the rates of metastases are 41.8% (38/91) in IMSC-LNs, 63.7% (58/91) in ILSC-LNs, 2.2% (2/91) in IIC-LNs, 12.1% (11/91) in TMMIC-LNs and 24.2% (22/91) in CSC-LNs, respectively. IMSC-LNs metastases are more frequent in estrogen-receptor (ER) positive (P=0.043, OR=0.401, 95%CI=0.166-0.971), the right breast cancer (P=0.036, OR=2.743, 95%CI=1.069-7.040) and the non-triple-negative subtype (P=0.020, OR=5.172, 95%CI=1.296-20.651). In addition, the predictive factors of ILSC-LNs metastases are location in upper inner quadrant (P=0.010, OR=0.159, 95%CI=0.039-0.650), lymphatic vessel invasion (P=0.006, OR=0.194, 95%CI=0.060-0.624) and vascular invasion (P=0.021, OR=0.273, 95%CI=0.090-0.825). ILSC-LNs were found to have a high risk of clavicular lymph nodes metastases in breast cancer. Moreover, ER-positive, right breast cancer, non-triple-negative subtype, location in upper inner quadrant and vessel carcinoma embolus were hopeful to predict metastases of clavicular lymph nodes, which could provide significant evidence for individualized clinical target volume delineation on breast cancer.

Adjuvant radiotherapy of regional lymph nodes in breast cancer - a meta-analysis of randomized trials

BackgroundRadiotherapy (RT) improves overall survival (OS) of breast cancer patients after breast conserving surgery and after mastectomy in patients with involved lymph nodes (LN). The contribution of RT to the regional LN to this survival benefit was poorly understood. Recently, the results of three large randomized trials addressing this question have become available.Material and methodsThe published abstracts (full publication pending) of the MA.20 (n=1832) and the EORTC 22922–10925 (EORTC) (n=4004) trial and the full publication of the French trial (n=1334) were basis of the meta-analysis. Main eligibility criteria were positive axillary LN (all trials), LN negative disease with high risk for recurrence (MA.20), and medial/central tumor location (French, EORTC). The MA.20 and the EORTC trial tested the effect of additional regional RT to the internal mammary (IM) LN and medial supraclavicular (MS) LN, whereas in the French trial all patients received RT to the MS-LN and solely RT to the IM-LN was randomized. Primary endpoint was OS. Secondary endpoints were disease-free survival (DFS) and distant metastasis free survival (DMFS).ResultsRegional RT of the MS-LN and the IM-LN (MA.20 and EORTC) resulted in a significant improvement of OS (Hazard Ratio (HR) 0.85 (95% CL 0.75 - 0.96)). Adding the results of the French trial and using the random effects model to respect the different design of the French trial, the effect on OS of regional radiotherapy was still significant (HR 0.88 (95% CL 0.80 - 0.97)). The absolute benefits in OS were 1.6% in the MA.20 trial at 5 years, 1.6% in the EORTC trial at 10 years, and 3.3% in the French trial at 10 years (not significant in single trials). Regional radiotherapy of the MS-LN and the IM-LN (MA.20 and EORTC) was associated with a significant improvement of DFS (HR 0.85 (95% CL 0.77 - 0.94)) and DMFS (HR 0.82 (95% CL 0.73 - 0.92)). The effect sizes were not significantly different between trials for any end point.ConclusionAdditional regional radiotherapy to the internal mammary and medial supraclavicular lymph nodes statistically significantly improves DFS, DMFS, and overall survival in stage I-III breast cancer.

6N Irradiation of the internal mammary and medial supraclavicular lymph node chain in stage I to III breast cancer: state of the day of EORTC phase III trial 22922/10925 with 4004 patients

Benign prostatic hyperplasia (BPH) is the leading cause of Lower Urinary Tract Symptoms (LUTS) in men worldwide. Urinary frequency, nocturia and incomplete emptying are common symptoms experienced by men with BPH, which significantly reduce their quality of life. Treatment for this dysfunction includes surgical and non-surgical modalities such as watchful waiting, lifestyle modification and medication. Historically, Transurethral Resection of the Prostate (TURP) had been considered the gold standard mainstay of treatment; however, in recent years, minimally invasive techniques which offer similar outcomes, fewer complications and cost-effectiveness have gained popularity. Rezum, is a relatively new minimally invasive modality used to treat BPH which has been recommended for prostate volumes of ≤80 cc. Herein, we present a successful case of managing BPH in a middle-aged patient with a prostate volume of 186 cc.

Conformal Locoregional Breast Irradiation with an Oblique Parasternal Photon Field Technique

We evaluated an isocentric technique for conformal irradiation of the breast, internal mammary, and medial supra-clavicular lymph nodes (IM-MS LN) using the oblique parasternal photon (OPP) technique. For 20 breast cancer patients, the OPP technique was compared with a conventional mixed-beam technique (2D) and a conformal partly wide tangential (PWT) technique, using dose-volume histogram analysis and normal tissue complication probabilities (NTCPs). The 3D techniques resulted in a better target coverage and homogeneity than did the 2D technique. The homogeneity index for the IM-MS PTV increased from 0.57 for 2D to 0.90 for PWT and 0.91 for OPP (both p < 0.001). The OPP technique was able to reduce the volume of heart receiving more than 30 Gy (V 30), the cardiac NTCP, and the volume of contralateral breast receiving 5 Gy (V 5) compared with the PWT plans (all p < 0.05). There is no significant difference in mean lung dose or lung NTCP between both 3D techniques. Compared with the PWT technique, the volume of lung receiving more than 20 Gy (V 20) was increased with the OPP technique, whereas the volume of lung receiving more than 40 Gy (V 40) was decreased (both p < 0.05). Compared with the PWT technique, the OPP technique can reduce doses to the contralateral breast and heart at the expense of an increased lung V 20.

Toxicity at three years with and without irradiation of the internal mammary and medial supraclavicular lymph node chain in stage I to III breast cancer (EORTC trial 22922/10925)

Introduction. The EORTC 22922/10925 trial investigated the potential survival benefit and toxicity of elective irradiation of the internal mammary and medial supraclavicular (IM-MS) nodes Accrual completed in January 2004 and first results are expected in 2012. We present the toxicity reported until year 3 after treatment. Patients and methods. At each visit, toxicity was reported but severity was not graded routinely. Toxicity rates and performance status (PS) changes at three years were compared by χ2 tests and logistic regression models in all the 3 866 of 4 004 patients eligible to the trial who received the allocated treatment. Results. Only lung (fibrosis; dyspnoea; pneumonitis; any lung toxicities) (4.3% vs. 1.3%; p < 0.0001) but not cardiac toxicity (0.3% vs. 0.4%; p = 0.55) significantly increased with IM-MS treatment. No significant worsening of the PS was observed (p = 0.79), suggesting that treatment-related toxicity does not impair patient's daily activities. Conclusions. IM-MS irradiation seems well tolerated and does not significantly impair WHO PS at three years. A follow-up period of at least 10 years is needed to determine whether cardiac toxicity is increased after radiotherapy.

WE-C-AUD B-10: Which Patients Benefit From Prospective Gating in Treatment for Loco-Regional Breast Irradiation - a Radiobiological Assessment

Purpose: To determine a selection procedure based on radiobiological parameters to triage patients that benefit maximally from the use of free breathing gating in inspiration during treatment of the breast, internal mammary and medial supraclavicular lymph nodes. Methodology: Twenty patients undergoing external treatment to the breast were prospectively selected in this study, 10 patients with involvement in the right breast, and 10 in the left‐hand side. All patients underwent a classical non‐gated CT scan, followed by a CT scan using prospective gating with coached breathing. To perform prospective gating a large bore Siemens Sensation Open™ was utilized, adapted to work with the Varian RPM™ gating system, which is also installed on our Varian Linacs. For each patient, dose distributions for the same field setup were calculated on each CT‐scan. Differential DVH's for heart and lung, were analyzed providing an NTCP using a serial model with parameters: s=1, gamma=1.28, and D50=52.3 for the heart (predicting an increased risk of late cardiac mortality), and s=0.06, gamma=0.90, and D50=34.0 for the lung respectively (predicting clinical radiation pneumonitis). Results: The mean NTCP for the heart for all patients was 0.80% for a non‐‐gated treatment and was reduced to 0.26% in gated treatments. This improvement was significant (p=0.0008). Five patients had a reduction of NTCP of 1% or more for heart complications. All of these patients were treated to the left breast, but not all left breast patients seemed to benefit. For lung NTCP overall improvement (p=0.0006) could be shown, reducing mean NTCP from 2.1% to 1.4%. Conclusion: We have shown that it is possible to have an objective criterium to apply free breathing gating for breast cancer patients resulting in an effective and economically acceptable use of machine time for gating.

Radiotherapy effects on systolic myocardial function detected by strain rate imaging in a left-breast cancer patient

Forty-eight-year old woman with left-sided mastectomy due to breast cancer received radiotherapy (RT) to the chest wall by a direct electron field. The internal mammary and medial supraclavicular lymph nodes were also irradiated with an anterior mixed photon–electron field. The radiation field was planned using a patient-specific treatment planning computed tomography (CT). Radiation dose was 50 Gy in 25 fractions. …

Quality Assurance in the EORTC Randomized Trial 22922/10925 Investigating the Role of Irradiation of the Internal Mammary and Medial Supraclavicular Lymph Node Chain Works

A quality assurance (QA) program in conjunction with the EORTC trial investigating the role of adjuvant internal mammary and medial supraclavicular irradiation in stage I-III breast cancer is presented. The results of a dummy run procedure and of an individual case review are compared to each other. The effects of recommendations based on QA procedures on the protocol compliance are evaluated. Prior to protocol activation all participating institutes were asked to produce treatment plans according to the guidelines of the protocol based on manual outlines of an average patient. Thereafter, they were asked to provide data on each of their first six randomized patients. The dummy run provided a lot of information on specific treatment techniques. In the individual case review, additional patient- and tumor-related data were collected, showing the use of anatomic information for treatment planning. A comparison between both procedures revealed that the individual case reports concurred more accurately with protocol guidelines than the dummy run. It was observed that the number of systematic protocol deviations was substantially decreased in trial patients compared to the dummy run case. Therefore, it is concluded that this extensive QA program had a positive effect on the consistency of all institutes participating in the trial.

Economic consequence of local control with radiotherapy: Cost analysis of internal mammary and medial supraclavicular lymph node radiotherapy in breast cancer

To investigate the financial implications of radiotherapy (RT) to the internal mammary and medial supraclavicular lymph node chain (IM-MS) in postoperative breast cancer. A cost-effectiveness and cost-utility analysis were performed, using Markov models, comparing the early and delayed costs and effects of IM-MS during a 20-year time span from a societal viewpoint. The outcome estimates were based on Level I evidence from postoperative RT literature and the cost estimates on the standard practice of the Leuven University Hospitals, with the RT costs derived from an activity-based costing program developed in the department. On the basis of the assumptions of the model and seen during a 20-year time span, primary treatment including IM-MS RT results in a cost savings (approximately 10,000) compared with a strategy without RT. Because IM-MS RT also results in better clinical effectiveness and greater quality of life, the treatment with IM-MS dominates the approach without IM-MS. Sensitivity analyses confirmed the robustness of these results in all tested circumstances. Although threshold values were found for the cost of IM-MS, the cost at relapse, and the quality of life after treatment, these were substantially different from the baseline estimates, indicating that it is very unlikely that omitting IM-MS would become superior. This ex-ante cost evaluation of IM-MS RT showed that the upfront costs of locoregional RT are easily compensated for by avoiding the costs of treating locoregional and distant relapse at a later stage. The cost-sparing effect of RT should, however, be evaluated for a sufficiently long time span and is most specifically found in tumors with a rather slow natural history and a multitude of available systemic treatments at relapse, such as breast cancer.

427 Poster Could radiotherapy to the internal mammary and medial supra clavicular lymph node chain (IM-MS) be cost-effective?

427 Poster Could radiotherapy to the internal mammary and medial supra clavicular lymph node chain (IM-MS) be cost-effective?

A glance on quality assurance in EORTC study 22922 evaluating techniques for internal mammary and medial supraclavicular lymph node chain irradiation in breast cancer

Purpose: To evaluate the irradiation techniques used for the irradiation of the internal mammary and medial supraclavicular lymph node chain (IM-MS) in the EORTC 22922 study, which evaluates its impact on survival in stage I–III breast cancer patients with axillary node invasion and/or central or medial location of the primary tumour. Materials and methods: The analysis was performed based on the dummy run data of the Quality Assurance Programme of the study. A standard irradiation technique was proposed within the study protocol, and the use of other treatment set-up techniques was allowed. Results: By March 2000, 39 centres from 12 different countries had participated in the study; 32 of these had already fulfilled the dummy run procedure. No centres had to be excluded from the study. Seventy-eight percent of the centres are using the standard irradiation technique, 64% of these with minor variations. Twenty-two percent of the centres developed an alternative irradiation technique. The remarks to the centres using the standard set-up were most often related to the junction problem and the possible under- or overdosage in the target volumes. The remarks to the centres with alternative techniques most often concerned the possible enhanced dose to the lungs and the heart. Conclusion: In a multi-centre trial an easy irradiation technique applicable in a large number of centres should be provided. A quality assurance programme allows early detection of possible problems with treatment planning and delivery. The analysis of the dummy run data showed that if the recommendations of the Quality Assurance Committee are applied, both standard and alternative IM-MS irradiation techniques produce acceptable dose distributions.

Influence of systemic therapy on pulmonary function tests in breast cancer patients irradiated to the internal mammary and medial supraclavicular lymph node chain

Influence of systemic therapy on pulmonary function tests in breast cancer patients irradiated to the internal mammary and medial supraclavicular lymph node chain

Quality assurance in the EORTC phase III randomised trial 22922/10925 investigating the role of internal mammary and medial supraclavicular lymph node chain irradiation in stage I–III breast cancer: A report on the dummy run

Quality assurance in the EORTC phase III randomised trial 22922/10925 investigating the role of internal mammary and medial supraclavicular lymph node chain irradiation in stage I–III breast cancer: A report on the dummy run

Low risk of locoregional recurrence of primary breast carcinoma after treatment with a modification of the Halsted radical mastectomy and selective use of radiotherapy

The purpose of the current study was to evaluate the locoregional recurrence rate after treatment of patients with operable breast carcinoma with a modification of the Halsted radical mastectomy and the selective use of radiotherapy and to identify risk factors for locoregional recurrence. Between 1979-1987, 691 consecutive patients underwent mastectomy after a negative biopsy of the axillary apical lymph nodes. The median age of the patients was 59 years (range, 26-89 years). The clinical tumor size was < 2 cm in 72 patients, 2-5 cm in 387 patients, and >5 cm in 169 patients; 16 patients had a T4 tumor. Surgery was comprised of a modification of the Halsted radical mastectomy, including at least part of the pectoralis major muscle and the entire pectoralis minor muscle, in 573 patients; 303 patients had positive axillary lymph nodes. Adjuvant radiotherapy to the chest wall and regional lymph nodes was given to 74 patients, whereas an additional 414 patients underwent irradiation to the internal mammary and medial supraclavicular lymph nodes. The median follow-up was 91 months. The actuarial overall survival rate was 82% at 5 years and 63% at 10 years. The 10-year chest wall and regional lymph node control rates, including patients with prior distant failures, were 95% and 94%, respectively. The only two significant prognostic factors for locoregional recurrence on multivariate analysis were lymph node status and pathologic tumor size. Excellent locoregional control can be achieved with a modified technique of radical mastectomy in patients with negative apical biopsy and the selective use of comprehensive radiotherapy. These results may serve as a reference outcome for comparison with other locoregional treatment strategies.