Mammary Chain Irradiation Research Articles

Concurrent chemo-radiotherapy in the treatment of early breast cancer: Current status

Concurrent chemo-radiotherapy (CCRT) in early cancer was investigated by few authors and remains controversial. This treatment is more commonly used for locally advanced cancer and showed high rate of complete pathological response. A search of articles published in English literature, between 1980 and November 2012, was conducted on Medline using the following terms: breast cancer, chemotherapy, radiotherapy, and Trastuzumab. We identified five phase I/II trials and three randomized phase three trials evaluating concurrent chemoradiotherapy in the adjuvant of cancer. In patients with early cancer having positive lymph nodes, phases III clinical trials showed that CCRT improved local control after conservative surgery. However, these randomized trials used non-standard regimen: Cyclophosphamide, methotrexate and fluorouracil (CMF) or fluorouracil, mitoxantrone and cyclophosphamide (FNC). In addition, in phases II clinical trials, concurrent use of taxanes and anthracycline with standard whole-breast irradiation showed high rate of toxicity: Pulmonary toxicity with taxane; and cardiac and skin toxicity with anthracycline. Consequentely, CCRT is not be used in practice because of concerns of toxicity with the standard drugs (anthracyclines and taxanes) and radiation. Anthracyclines with partial irradiation (PBI) was feasible according to one phase I clinical trial, and should be investigated in randomized clinical trials. Concurrent Trastuzumab plus radiotherapy is safe and can be used in HER2-positive cancer; in this case, cardiac volume sparing and patient selections for internal mammary chain irradiation are highly recommended. The present paper aimed to review the current data evaluating the efficacy and safety of CCRT in early cancer.

Lymphoscintigraphy Can Select Breast Cancer Patients for Internal Mammary Chain Radiotherapy

Given the risk of undesired toxicity, prophylactic internal mammary (IM) chain irradiation should be offered only to patients at high risk of occult involvement. Lymphoscintigraphy for axillary sentinel node biopsy might help in selecting these patients. We reviewed published studies with the following selection criteria: ≥ 300 breast cancer patients referred for axilla sentinel node biopsy; scintigraphy performed after peritumoral or intratumoral tracer injection; IM biopsy in the case of IM drainage; and axilla staged routinely independent of IM status. Six prospective studies, for a total of 3,876 patients, fulfilled the inclusion criteria. Parasternal drainage was present in 792 patients (20.4%). IM biopsy was performed in 644 patients and was positive in 111 (17.2%). Of the positive IM biopsies, 40% were associated with tumors in the lateral breast quadrants. A major difference in the IM positivity rate was found according to the axilla sentinel node status. In patients with negative axilla, the IM biopsy was positive in 7.8% of cases. In patients with positive axilla, however, the IM biopsy was positive in 41% (p < .00001). Because biopsy of multiple IM hot nodes is difficult, the true risk could be even greater, probably close to 50%. Patients with IM drainage on lymphoscintigraphy and a positive axilla sentinel node have a high risk of occult IM involvement. These women should be considered for IM radiotherapy.

Genetic variants in TGFβ-1 and PAI-1 as possible risk factors for cardiovascular disease after radiotherapy for breast cancer

Background and purposeIt has been established that radiotherapy can increase cardiovascular disease (CVD) risk. Genetic variants, which play a role in the tissue, damage response and angiogenesis regulating TGFβ pathway might give us insight into the mechanisms underlying radiation-induced CVD. We examined the effects of two polymorphisms, TGFβ1 29C>T and PAI-1 5G>4G, on CVD incidence. Materials and methodsThis retrospective cohort study included 422 10-year breast cancer survivors, aged <50years at diagnosis, treated between 1977 and 1995. We collected information on treatment, oncological follow-up, CVD, CVD risk factors and genotypes. ResultsDuring a mean follow-up of 19.4years, 61 patients developed CVD. Internal mammary chain (IMC) irradiation, exposing a part of the heart to radiation, was associated with a hazard ratio of 2.36 (95% CI: 1.27–4.37, p=0.01) compared to no IMC irradiation. Compared to the C/C+C/T genotype, the T/T genotype of the TGFβ1 polymorphism was associated with hazard ratios of 1.79 (0.99–3.26, p=0.06) and 1.74 (0.90–3.34, p=0.10) in the total and IMC-irradiated group, respectively. We found no evidence for an association between PAI-1 5G>4G and CVD risk. ConclusionOur study suggests there might be an association between the TGFβ1 29C>T polymorphism and CVD risk in long-term breast cancer survivors.

The acute skin and heart toxicity of a concurrent association of trastuzumab and locoregional breast radiotherapy including internal mammary chain: A single-institution study

Background To evaluate the skin and heart toxicity of a concurrent adjuvant trastuzumab-radiotherapy for breast cancer (BC), especially in the case of internal mammary chain (IMC) irradiation. Material and methods Prospective study of 106 patients treated between 06/2003 and 03/2007 by concurrent trastuzumab-radiotherapy for non-metastatic BC. Left ventricular ejection fractions (LVEF) was assessed at baseline, before and after radiotherapy and then every 4–6 months. All toxicities were evaluated using CTCAEV3. Results Median age was 52 years (25–76). Chemotherapy with anthracycline was administered in 92% of patients. All patients received trastuzumab every three weeks (8 mg/kg followed by 6 mg/kg) for a median duration of 12 months (3-40). The IMC was irradiated in 83% of patients. There were: 87 grade 1, 14 grade 2 and 2 grade 3 skin reactions. There were 13 oesophagitis: 9 grade 1; 3 grade 2, and 1 grade 3. Out of 101 patients with assessments after 6 months, late telangiectasia grade 1 occurred in 5 patients, local pain grade 1 in 19 patients and grade 2 in 3 patients, fibrosis grade 1 in 16 patients. A reversible grade ⩾2 left ventricular systolic dysfunction occurred in 6 patients. Conclusion In this prospective study of breast cancer patients treated with trastuzumab-radiotherapy with, in most cases, anthracycline-based chemotherapy and IMC irradiation, both the rate of abnormal LVEF after concurrent trastuzumab-radiotherapy and the skin toxicity were deemed acceptable. Further follow-up is needed.

Ten-year Results of a Randomized Trial of Internal Mammary Chain Irradiation after Mastectomy

1 Ten-year Results of a Randomized Trial of Internal Mammary Chain Irradiation after Mastectomy P. Romestaing, A. Belot, C. Hennequin, J. Bosset, P. Maingon, J. Dubois, N. Bossard, J. Gerard Centre De Radiotherapie Charcot, Ste Foy Les Lyon, France, Service De Biostatistiques Des Hospices Civils De Lyon, Lyon Cedex, France, Service De Radiotherapie Hopital St. Louis, Hopitaux De Paris, France, Service De Radiotherapie, Besancon, France, Service De Radiotherapie, Dijon, France, Service De Radiotherapie, Montpellier, France, Service De Radiotherapie, Nice, France

Can the sentinel lymph node technique affect decisions to offer internal mammary chain irradiation?

Identification of the sentinel lymph node (SLN) for small mammary tumours (cT1N0) sometimes leads to detection of internal mammary chain (IMC) drainage. This information is often ignored by physicians. The present study sought to determine the frequency with which an internal mammary SLN was identified by peritumoral injection of radioactive tracer, and then to determine the patients in whom identification of an internal mammary SLN could have an impact on the radiation treatment plan. Between March 2002 and March 2008, 622 SLN biopsies performed in a cohort of 608 patients were analysed. Technetium-labelled nanocolloids were administered via three peritumoral injections, completed by a deep prepectoral injection, with the entire procedure performed under echographic guidance. The SLN was identified in 607 of the 622 patients, including 174 (28.7%) in the IMC. A total of 161 successful internal mammary biopsies were performed. Of the 622 patients, 18 showed SLN involvement in the IMC. In 7 of these patients, only the internal mammary SLN was affected. Prophylactic irradiation of the IMC was indicated in 376 patients, but only in 18 (4.8%) of these patients was there effectively IMC involvement; internal mammary SLN biopsy failed in 7 patients (1.9%). SLN detection by peritumoral injection, combined with the systematic removal of the internal mammary SLN, enabled the involvement of this region to be found in a nonnegligible number of patients. Such information should make it possible to personalize treatment for patients with stage cT1 mammary cancer and thereby avoid needless internal mammary radiation therapy in a large number of patients (93.4% in our study).

Acute cardiotoxicity with concurrent trastuzumab and radiotherapy including internal mammary chain nodes: A retrospective single-institution study

Purpose To examine the acute cardiotoxicity of internal mammary chain (IMC) irradiation with concurrent trastuzumab. Materials and Methods Clinical and cardiac function data were collected on 59 patients with early breast cancer who were treated with adjuvant trastuzumab and chemotherapy with or without radiotherapy (often including IMC) at BC Cancer Agency in 2005. Results Forty-four of fifty-nine patients received adjuvant radiotherapy (RT). Thirteen had left-sided IMC RT. For left-sided RT, IMC inclusion increased the mean percentage dose to 5% of the heart, but the mean doses to 50% and 90% of the heart were similar. Median baseline left ventricular ejection fraction (LVEF) was 62% and similar in all groups. Median absolute decrease in LVEF after RT was 4%, which was not significantly different according to side or inclusion of IMCs. Trastuzumab was stopped in 11 of 59 patients (18.6%) due to decrease in LVEF. After median follow up of 15 months, three patients developed clinical congestive heart failure, none of whom received left-sided IMC RT. Conclusions There was no excess acute cardiotoxicity observed with the combination of left-sided IMC irradiation and concurrent trastuzumab.

52 Cardiac tolerance with concurrent trastuzumab and internal mammary chain irradiation

52 Cardiac tolerance with concurrent trastuzumab and internal mammary chain irradiation

Clinical application of a OneDose™ MOSFET for skin dose measurements during internal mammary chain irradiation with high dose rate brachytherapy in carcinoma of the breast

In our earlier study, we experimentally evaluated the characteristics of a newly designed metal oxide semiconductor field effect transistor (MOSFET) OneDose™ in-vivo dosimetry system for Ir-192 (380 keV) energy and the results were compared with thermoluminescent dosimeters (TLDs). We have now extended the same study to the clinical application of this MOSFET as an in-vivo dosimetry system. The MOSFET was used during high dose rate brachytherapy (HDRBT) of internal mammary chain (IMC) irradiation for a carcinoma of the breast. The aim of this study was to measure the skin dose during IMC irradiation with a MOSFET and a TLD and compare it with the calculated dose with a treatment planning system (TPS). The skin dose was measured for ten patients. All the patients' treatment was planned on a PLATO treatment planning system. TLD measurements were performed to compare the accuracy of the measured results from the MOSFET. The mean doses measured with the MOSFET and the TLD were identical (0.5392 Gy, 15.85% of the prescribed dose). The mean dose was overestimated by the TPS and was 0.5923 Gy (17.42% of the prescribed dose). The TPS overestimated the skin dose by 9% as verified by the MOSFET and TLD. The MOSFET provides adequate in-vivo dosimetry for HDRBT. Immediate readout after irradiation, small size, permanent storage of dose and ease of use make the MOSFET a viable alternative for TLDs.

Estudio comparativo de las diferentes vías de administración del radiotrazador para la localización del ganglio centinela en el cáncer de mama

To assess the results of Sentinel Lymph Node (SLN) detection in breast cancer patients depending on the radiotracer injection route, especially evaluating which route that makes it possible to identify the highest percentage of SLNs and its detection in the inner mammary chain. We prospectively studied 120 breast cancer patients. Three groups of 40 patients each were established depending on the radiotracer injection route. 1) Subdermal or subareolar route: 18 T1 and 22 T2, mean tumor diameter size of 1.76 cm. 2) Peritumoral route: 16 T1 and 24 T2, mean tumor diameter size of 1.86 cm. 3) Intratumoral route: 20 T1 and 20 T2, mean tumor diameter size of 1.61 cm. The day before surgery, a lymphoscintigraphic study was performed in all cases and intraoperative SLN resection was carried out with the aid of a hand-held gamma probe. The SLN was identified in 38/40 cases (95%) of group 1, in 35/40 cases (88%) of group 2 and in 38/40 cases (95%) of group 3. No SLNs in the mammary chain were observed in patients who underwent subdermal/subareolar injection of the radiotracer. On the other hand, SLNs were visualized in this location in 4/35 patients with peritumoral injection (11%) and in 8/38 patients with intratumoral injection (21%). The superficial (subdermal, subareolar) injection technique is more suitable when an unnecessary lymphadenectomy has to be prevented in cases without axillary metastases. The deeper injection technique (peritumoral, intratumoral) should be use when, moreover, we seek accurate staging or plan non-systematic mammary chain irradiation.

Breast radiotherapy with inclusion of internal mammary nodes: a comparison of techniques with three-dimensional planning

Purpose: To compare the partially wide tangent (PWT) technique of breast and internal mammary chain irradiation with photon/electron (P/E) and standard tangent (ST) techniques in terms of dose homogeneity within breast and the dose to critical structures such as the heart and lung. Methods and Materials: Sixteen left breast cancer patients underwent CT simulation. The breasts, lungs, heart, and internal mammary chain were contoured and treatment plans generated on a three-dimensional planning system (Helax-TMS). Results: The mean dose to the left breast volume with the ST, P/E, and PWT techniques was 94.7%, 98.4%, and 96.5%, respectively ( p = 0.029). The left lung received the lowest mean dose with the ST technique (13.9%) compared with PWT (22.8%) and P/E (24.3%). The internal mammary chain volume was most consistently treated with the PWT (mean dose 99%) vs. P/E (86%) and ST (38.4%) techniques. The heart received the least dose with ST (mean dose 6.7%) vs. PWT (10.3%) and P/E (19%). The PWT treated the greatest amount of contralateral breast (mean dose 5.8%) vs. ST (3.2%) vs. P/E (2.8%). Conclusion: The PWT technique treats the internal mammary chain with acceptable toxicity to major organs, especially the heart, and with reasonable dose homogeneity in patients with mastectomy or intact breasts.

"Standards, Options and Recommendations 2001" for radiotherapy in patients with non-metastatic infiltrating breast cancer. Update. National Federation of Cancer Campaign Centers (FNCLCC)

The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of french cancer centers (FNCLCC), the 20 french cancer centers, and specialists from french public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. To develop clinical practice guidelines for non metastatic breast cancer patients according to the definitions of the Standards, Options and Recommendations project. Data were identified by searching Medline, web sites, and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 148 independent reviewers. This article presents the chapter radiotherapy resulting from the 2001 update of the version first published in 1996. The modified 2001 version of the standards, options and recommendations takes into account new information published. The main recommendations are: (1) Breast irradiation after conservative surgery significantly decrease the risk of local recurrence (level of evidence A) and the decrease in the risk of local recidive after chest wall irradiation is greater as the number of risk factors for local recurrence increases (level of evidence A). (2) After conservative surgery, a whole breast irradiation should be performed at a minimum dose of 50 Gy in 25 fractions (standard, level of evidence A). (3) A boost in the tumour bed should be performed in women under 50 years, even if the surgical margins are free (standard, level of evidence B). (4) Internal mammary chain irradiation is indicated for internal or central tumours in the absence of axillary lymph node involvement (expert agreement) and in the presence of lymph node involvement (standard, level of evidence B1). (5) Sub- and supra-claviculr lymph node irradiation is indicated in patients with axillary node involvement (standard, level of evidence B1).

Review of internal mammary chain irradiation in breast cancer

The aim was to assess the effectiveness of and indications for irradiation of the internal mammary chain (IMC) in the treatment of breast cancer based on a review of the literature. A computerized literature search was performed of the MEDLINE database from 1966 to March 1998. The data retrieved were ranked into levels of evidence as per convention. There was no Level I evidence found. Six randomized controlled trials and nine retrospective series were found pertaining to early stage breast cancer. Although some retrospective data suggested that IMC irradiation improved survival in mediocentral and axillary node-positive tumours, this was not supported by the randomized data. Two randomized trials were identified in high risk operable breast cancer. One of these showed a survival advantage to post-mastectomy irradiation, but the contribution of IMC irradiation to this could not be delineated. Based on the best current evidence, there is no advantage to elective IMC irradiation. The only indication is for positive IMC nodes where the management aim is palliative. The ongoing EORTC randomized trial may provide the definitive answer.

EORTC randomised phase III trial 22922/10925 investigating the role of internal mammary chain (IMC) irradiation in stage I-III breast cancer: A quality assurance report on the dummy run

EORTC randomised phase III trial 22922/10925 investigating the role of internal mammary chain (IMC) irradiation in stage I-III breast cancer: A quality assurance report on the dummy run

The Long-Term Effects of Internal Mammary Chain Irradiation and Its Role in the Vascular Supply of the Pedicled Transverse Rectus Abdominis Musculocutaneous Flap Breast Reconstruction

With an increase in breast-sparing surgery and adjuvant radiotherapy, there has been a concomitant increase in the complexity of breast reconstruction. The effects of radiotherapy on the internal mammary artery were evaluated with respect to flap viability for conventional transverse rectus abdominis musculocutaneous breast reconstruction using the irradiated rectus muscle. Twenty-eight women who received postoperative irradiation for breast cancer were studied. All women had unilateral irradiation, and evaluation of the internal mammary arteries was performed at least 1 year after the completion of radiotherapy to allow for fibrosis and long-term vascular changes. Examination of the internal mammary artery (upper and lower chains) was performed using color Doppler sonography to assess vessel diameter, peak systolic velocity, and blood flow. The nonirradiated side was compared to the radiated internal mammary artery as an internal control. Based on the details of prior radiotherapy, the 28 women were designated into two groups. Group I included 14 women with radiation portals that specifically treated the internal mammary chain; the average dose to the internal mammary chain was 47.44 Gy. Group II comprised 14 patients that received tangential portals that did not directly target the internal mammary chain region; the average radiation dose was 48.21 Gy to the chest wall. No statistical difference was observed in group I between the irradiated and nonirradiated side for vessel diameter (p = .8631) or peak systolic velocity (p = .2646). However, an increase in blood flow on the irradiated side was significant (p = .0321).(ABSTRACT TRUNCATED AT 250 WORDS)

Tangential breast irradiation with or without internal mammary chain irradiation: results of a randomized trial

A prospective randomized study was made of 270 patients with unilateral stage I or II invasive breast cancer treated by segmental resection, axillary dissection and radiation at the University Hospital of Tampere, Finland, between 1989 and 1991. The aim of the study was to determine whether there is any advantage or disadvantage if the internal mammary chains (IMC) are included in the radiation target volume. The medial and lateral two-field technique was used and the target volumes were determined randomly either to include the internal mammary chain (IMC-RT) or not (no-IMC-RT). The prevalence of radiation pneumonitis was 16% and there was no significant difference between the IMC- and no-IMC-groups (18 vs. 14%). Skin reactions were equal in both groups. Lung fibrosis was more common in the IMC-RT group. In conclusion: radiation of internal mammary chain after conservative surgery does not lead to an increase in clinically important skin or pulmonary complications. Whether it prevents recurrences or new primaries of the opposite breast is too early to say because of the short follow-up time.

Radiotherapy Alone in Breast Cancer: Analysis of Tumor Parameters, Tumor and Lymph Node Doses, Lymph Node Control, Distant Metastasis, and Survival Rates—The Experience of the Gustave‐Roussy Institute and the Princess Margaret Hospital

AbstractThis retrospective analysis involved 453 breast cancer patients treated by radiotherapy alone at the Princess Margaret Hospital and at the Institut Gustave‐Roussy. These patients either had operable tumors, but were unfit for general anesthesia, or had inoperable tumors due to local contraindications to surgery. Results were analyzed according to lymph node response, lymph node recurrence rate, distant metastasis rate, survival rate, tumor size, clinical N category, age, tumor dose, axillary dose, and internal mammary chain irradiation. Multivariate analysis permitted the definition of a risk score for axillary lymph node recurrence (RSLN) according to two independent factors: tumor size and clinical N category. It was shown that the RSLN was a good single composite prognostic factor for lymph node control. Increase in axillary dose gave a similar effect on the axillary lymph node recurrence relative risk for all the RSLN groups. According to the slope of the axillary dose‐effect curve, it was deduced that a dose increase of 15 Gy can decrease the relative risk of lymph node recurrence 2‐fold. A similar slope was previously described for tumor dose and local control. A risk score for distant metastases (RSM) was calculated according to three independent prognostic factors: tumor size, clinical N category, and age. The RSM was not influenced by the tumor or the axillary dose but by the treatment of the internal mammary chain. Similar results were obtained for the risk score for death (RSD). The present data emphasize the role of the lymph node radiation dose in the lymph node control of locally advanced breast cancer. © 1993 Wiley‐Liss, Inc.

Acute cardiac effects of mediastinal irradiation: Assessment by radionuclide angiography

Mediastinal irradiation is considered as a long term cardiac risk factor, although no myocardial dysfunction can usually be documented during long term follow-up of the patients having undergone this treatment. We prospectively studied on 124 patients the early effects of irradiation on the myocardium using radionuclide angiography Left ventricular ejection fraction was measured at three different times: before starting the irradiation, 15 days after and more than 2 months after the end of the treatment. The patients were divided into four groups according to the type of irradiation received: M group of 53 patients (mediasteinal irradiation), L group of 33 patients (left mammary chain irradiation), R group of 25 patients (right mammary chain irradiation), C group for 13 control patients (irradiation field did not include the heart). Sixty-nine of these patients were treated by chemotherapy, including adriamycin in 48 of them. For all patients for whom the myocardium was included into the field of irradiation (M, L, and R) there is a significant fall of the Left ventricular ejection fraction 15 days after the end of treatment, with recovery after 2 months. This fall is not seen in controls. Patients who received adriamycin follow the same evolution, and there is no significant difference in the basal LVEF value nor in the magnitude of the fall.

Oesophageal Carcinoma Following Internal Mammary Chain Irradiation for Carcinoma of the Breast—a Report of Six Cases

Oesophageal Carcinoma Following Internal Mammary Chain Irradiation for Carcinoma of the Breast—a Report of Six Cases