Intraoperative radiotherapy (IORT) as a boost in patients with early-stage breast cancer -- acute toxicity

BACKGROUND: We report on acute toxicities as well as the early cosmetic outcome of patients receiving intraoperative radiotherapy (IORT) followed by whole-breast radiotherapy (WBRT) compared to patients treated with standard WBRT alone. PATIENTS AND METHODS: From 2/2002 until 2/2005, 84 breast cancer patients were treated with IORT during breast-conserving surgery (BCS) as a boost (20 Gy/50 kV X-rays) followed by WBRT. After wound healing, all IORT patients were treated with WBRT at a total dose of 46 Gy. For the purpose of comparison, 53 patients treated consecutively between 1/2003 and 12/2004 in our institution with BCS followed by WBRT at a total dose of 50-66 Gy, were analyzed. All patients had a defined followup schedule. Toxicities were prospectively documented using the CTC/EORTC Score. Cosmesis was evaluated after 6 months using a 1-4 score. RESULTS: Treatment was well tolerated with no grade 3/4 acute toxicity. Rare adverse effects following IORT included wound healing problems (2%), erythema grade I-II (3%), palpable seroma (6%) and mastitis (2-4%). The number of patients with induration of the tumor bed was comparably low. CONCLUSION: IORT with the IntrabeamTM system applied as a boost during BCS, followed by 46 Gy WBRT, exerts similar acute toxicity as standard WBRT. Further follow-up is needed to assess long-term toxicity and efficacy.     

Intraoperative radiotherapy (IORT) for breast cancer using the Intrabeam system

INTRODUCTION: Intraoperative radiotherapy (IORT) with low-energy X-rays (30-50 KV) is an innovative technique that can be used both for accelerated partial breast irradiation (APBI) and intraoperative boosting in patients affected by breast cancer. Immediately after tumor resection the tumor bed can be treated with low-distance X-rays by a single high dose. Whereas often a geographic miss in covering the boost target occurs with external beam boost radiotherapy (EBRT), the purpose of IORT is to cover the tumor bed safely. This report will focus on the feasibility and technical aspects of the Intrabeam device and will summarize our experience with side effects and local control. MATERIALS AND METHODS: Between February 2002 and June 2003 57 breast cancer patients, all eligible for breast conserving surgery (BCS), were treated at the Mannheim Medical Center with IORT using the mobile X-ray system Intrabeam. The patient population in this feasibility study was not homogeneous consisting of 49 patients with primary stage I or II breast cancer, seven with local recurrence after previous EBRT and one with a second primary in a previously irradiated breast. The selection criteria for referral for IORT included tumor size, tumor cavity size, margin status and absence of an extensive intraductal component. The previously irradiated patients with local recurrences and 16 others received IORT as single modality. In all other cases IORT was followed by EBRT with a total dose of 46 Gy in 2-Gy fractions. The intraoperatively delivered dose after tumor resection was 20 Gy prescribed to the applicator surface. EBRT was delivered with a standard two-tangential-field technique using linear accelerators with 6- or 18-MV photons. Patients were assessed every three months by their radiation oncologist or surgeon during the first year after treatment and every six months thereafter. Breast ultrasound for follow-up was done every six months and mammographies once yearly. Acute side effects were scored according to the CTC/EORTC score and late side effects according to the Lent-Soma classification. RESULTS: Twenty-four patients received IORT only; eight patients because they had received previous radiotherapy, 16 because of a very favorable risk profile or their own preference. Thirty-three patients with tumor sizes between 1 and 30 mm and no risk factors were treated by IORT as a boost followed by EBRT. The Intrabeam system was used for IORT. The Intrabeam source produces 30-50 KV X-rays and the prescribed dose is delivered in an isotropic dose distribution around spherical applicators. Treatment time ranged between 20 and 48 minutes. No severe acute side effects or complications were observed during the first postoperative days or after 12 months. One local recurrence occurred 10 months after surgery plus IORT followed by EBRT. In two patients distant metastases were diagnosed shortly after BCS. DISCUSSION: IORT with the Intrabeam system is a feasible method to deliver a single high radiation dose to breast cancer patients. As a preliminary boost it has the advantage of reducing the EBRT course by 1.5 weeks, and as APBI it might be a promising tool for patients with a low risk of recurrence. The treatment is well tolerated and does not cause greater damage than the expected late reaction in normal tissue.     

Intraoperative radiotherapy given as a boost for early breast cancer: long-term clinical and cosmetic results

PURPOSE: The standard radiotherapy (RT) of breast cancer consists of 50 Gy external beam RT (EBRT) to the whole breast followed by an electron boost of 10-16 Gy to the tumor bed, but this has several cosmetic disadvantages. Intraoperative radiotherapy (IORT) could be an alternative to overcome these. METHODS AND MATERIALS: We evaluated 50 women with early breast cancer operated on in a dedicated IORT facility. Median dose of 10 Gy was delivered using 9-MeV electron beams. All patients received postoperative EBRT (50 Gy in 2 Gy fractions). Late toxicity and cosmetic results were assessed independently by two physicians according to the Common Terminology Criteria for Adverse Event v3.0 grading system and the European Organization for Research and Treatment of Cancer questionnaires. RESULTS: After a median follow-up of 9.1 years (range, 5-15 years), two local recurrences were observed within the primary tumor bed. At the time of analysis, 45 patients are alive with (n = 1) or without disease. Among the 42 disease-free remaining patients, 6 experienced Grade 2 late subcutaneous fibrosis within the boost area. Overall, the scores indicated a very good quality of life and cosmesis was good to excellent in the evaluated patients. CONCLUSION: Our results confirm that IORT given as a boost after breast-conserving surgery is a reliable alternative to conventional postoperative fractionated boost radiation.     

Late radiation toxicity after intraoperative radiotherapy (IORT) for breast cancer: results from the randomized phase III trial TARGIT A

The randomized phase III trial TARGIT A showed non-inferiority regarding local control after intraoperative radiotherapy (IORT 20 Gy which was followed by whole breast radiotherapy (WBRT) in patients with risk factors only) in comparison to standard WBRT (50–56 Gy) after breast-conserving surgery in selected patients. This is the first analysis of long-term toxicities in the setting of TARGIT. Between 02/2002 and 12/2008, 305 patients were treated within TARGIT A (Arm A: n = 34 IORT, n = 20 IORT + WBRT for risk factors; Arm B WBRT: n = 55) or received IORT as a planned boost (control group: n = 196) at a single center. Toxicity was assessed according to the LENT SOMA scales. No significant differences were seen between Arm A and Arm B regarding fibrosis, breast edema, retraction, ulceration, lymphedema, hyperpigmentation, and pain. Arm A had significantly less telangiectases compared to Arm B (p = 0.049). In the subanalysis (Arm A IORT vs. Arm A IORT + WBRT vs. Arm B), fibrosis had a cumulative rate of 5.9 versus 37.5 versus 18.4 %, respectively (38.2 % IORT boost control group), at 3 years. No telangiectases were seen after IORT alone (0 % Arm A IORT vs. 17.5 % Arm A IORT + WBRT vs. 17.7 % Arm B). The hazard ratio of higher grade toxicity as first event was 0.46 (95 % CI, 0.26–0.83) for Arm A IORT as compared to Arm B (p = 0.010). No recurrences were seen after a median follow-up of 40 months (Arm A) and 42 months (Arm B). With its very low chronic skin toxicity rates and outstanding long-term results regarding toxicity and local control, IORT with 50 kV X-rays is a safe and effective method for treatment of selected breast cancer patients.     

Intraoperative radiotherapy given as a boost after breast-conserving surgery in breast cancer patients

Conventional radiotherapy after breast-conserving therapy is confined to 50-55 Gy external beam radiation therapy (EBRT) to the whole breast and 10-16 Gy external boost radiation to the tumour bed or brachytherapy to the tumour bed. Local recurrence rate after breast-conserving surgery varies between 5 and 18%. External boost radiation can partially miss the tumour bed and therefore can result in local failure. Intra-operative radiotherapy (IORT) as a high precision boost can prevent a 'geographical miss'. From October 1998 to December 2000, 156 patients with stage I and stage II breast cancer were operated upon in a dedicated IORT facility. After local excision of the tumour, the tumour bed was temporarily approximated by sutures to bring the tissue in the radiation planning target volume. A single dose of 9 Gy was applied to the 90% reference isodose with energies ranging from 4 to 15 MeV, using round applicator tubes 4-8 cm in diameter. After wound healing, the patients received additional 51-56 Gy EBRT to the whole breast. No acute complications associated with IORT were observed. In 5 patients, a secondary mastectomy had to be performed because of tumour multicentricity in the final pathological report or excessive intraductal component. 2 patients developed rib necroses. In 7 patients, wound healing problems occurred. After a mean follow-up of 18 months, no local recurrences were observed. Cosmesis of the breast was very good and comparable to patients without IORT. Preliminary data suggest that IORT given as a boost after breast-conserving surgery could be a reliable alternative to conventional postoperative fractionated boost radiation by accurate dose delivery and avoiding geographical misses, by enabling smaller treatment volumes and complete skin-sparing and by reducing postoperative radiation time by 7-14 days.     

早期乳腺癌保乳术后全乳大分割照射同步瘤床加量的临床分析

目的：观察早期乳腺癌保乳术后全乳大分割照射同步瘤床加量的短期疗效与不良反应。方法64例早期乳腺癌患者保乳术后行两野切线全乳照射,全乳腺照射40．5 Gy／15 f,单次剂量2．7 Gy／f,同步瘤床推量至48 Gy／15 f,单次剂量3．2 Gy／f,总疗程3周,观察分析患者局部复发情况、美容效果及不良反应。结果中位随访时间17月,随访率为100％,无局部复发情况发生。3例患者表现乳腺中度胀痛;Ⅰ、Ⅱ、Ⅲ级急性皮肤反应发生率分别为17．2％、4．7％、1．6％;Ⅰ级血小板下降发生率与Ⅰ～Ⅱ级中性粒细胞减少发生率分别为1．6％、4．7％;放疗完成后4、7月美容优良率分别为90．6％、87．5％。结论早期乳腺癌保乳术后全乳放疗同步瘤床加量的短期疗效与以往常规放疗方式相似,缩短放疗时间,不会增加皮肤不良反应及降低美容效果。     

Phase I study of intraoperative radiotherapy with photon radiosurgery system in children with recurrent brain tumors: preliminary report of first dose level (10 Gy)

PURPOSE: To describe the preliminary results after intraoperative radiotherapy (IORT) with the photon radiosurgery system in children with recurrent brain tumors treated at the first dose level (10 Gy) of a Phase I protocol. METHODS AND MATERIALS: A Phase I IORT dose escalation protocol was initiated at Children's Memorial Hospital to determine the maximal tolerated IORT dose in children with recurrent brain tumors. RESULTS: Fourteen children have received IORT thus far. Eight had been previously irradiated. Thirteen children had ependymoma. The median follow-up was 16 months. Three patients (21%) developed radiation necrosis on follow-up MRI scans 6 to 12 months after IORT. They had not been previously irradiated and had received 10 Gy to a depth of 5 mm. One required surgery and the other two had resolution of their lesions without treatment. All 3 patients were asymptomatic at the last follow-up. No other late toxicity was observed at the last follow-up visit. Eight patients (57%) had tumor control within the surgical bed after IORT. CONCLUSION: Our findings have demonstrated the safety and feasibility of IORT to a dose of 10 Gy to 2 mm in children with previously irradiated brain tumors. IORT to a dose of 10 Gy at 5 mm was associated with a greater complication rate.     

TARGIT-E(lderly) - Prospective phase II study of intraoperative radiotherapy (IORT) in elderly patients with small breast cancer

ABSTRACT: BACKGROUND: Patients [greater than or equal to] 70 years with small, low-risk breast cancer who are operated but not irradiated show local relapse rates around 4% after 4 years. With adjuvant whole breast radiotherapy (WBRT) the local relapse rate drops to 1% after 4 years under Tamoxifen (5). It has been demonstrated (6, 12) that the efficacy of radiotherapy of the tumor bed only in a selected group can be non-inferior to WBRT. METHODS: This prospective, multicentric single arm phase II study is based on the protocol of the international TARGIT-A study. The TARGIT-E study should confirm the efficacy of a single dose of intraoperative radiotherapy (IORT) in a well selected group of elderly patients with small breast cancer and absence of risk factors. Patients will receive IORT (20 Gy with Intrabeam system/Carl Zeiss) during breast conserving surgery. In presence of risk factors postoperative WBRT will be added to complete the radiotherapeutic treatment according to international guidelines. Endpoints are the local relapse rate (within 2 cm of the tumor bed), ipsilateral in breast relapse, cancer-specific and overall survival and contralateral breast cancer as well as documentation of quality of life and cosmetic outcome. The expected local relapse rates are 0.5/1/1.5% after 2.5/5/7.5 years, respectively. Discontinuation of the trial is scheduled if rates of local relapse rates rise to 3/4/6% after 2.5/5/7.5 years. Power calculations result in 540 patients with a calculated dropout rate of 20% and loss to follow-up of 20%, an alpha of 0.01 and a beta 0.05. There will be a pre- and a post-pathology stratum (n=270 each). DISCUSSION: It is a pragmatic trial in which each participating centre has the option to modify entry criteria and criteria for WBRT according to this core protocol after consultation with the steering committee and local ethics committee (e.g. size, free margins). Only centers with access to the Intrabeam system (Carl Zeiss) can recruit patients into the trial. Its aim is to confirm the efficacy and toxicity of IORT in a well selected collective of elderly patients with breast cancer.     

Ten-year results of accelerated hypofractionated adjuvant whole-breast radiation with concomitant boost to the lumpectomy cavity after conserving surgery for early breast cancer

Accelerated hypofractionated whole-breast radiotherapy (WBRT) is considered a standard therapeutic option for early breast cancer (EBC) in the postoperative setting after breast conservation (BCS). A boost to the lumpectomy cavity may further increase local control. We herein report on the 10-year results of a series of EBC patients treated after BCS with hypofractionated WBRT with a concomitant photon boost to the surgical bed over 4 weeks. Between 2005 and 2007, 178 EBC patients were treated with a basic course of radiotherapy consisting of 45 Gy to the whole breast in 20 fractions (2.25 Gy daily) with an additional boost dose of 0.25 Gy delivered concomitantly to the lumpectomy cavity, for an additional dose of 5 Gy. Median follow-up period was 117 months. At 10-year, overall, cancer-specific, disease-free survival and local control were 92.2% (95% CI 88.7–93.4%), 99.2% (95% CI 96.7–99.7%), 95.5% (95% CI 91.2–97.2%) and 97.3% (95% CI 94.5–98.9%), respectively. Only eight patients recurred. Four in-breast recurrences, two axillary node relapses and two metastatic localizations were observed. Fourteen patients died during the observation period due to other causes while breast cancer-related deaths were eight. At last follow-up, ≥G2 fibrosis and telangiectasia were seen in 7% and 5% of patients. No major lung and heart toxicities were observed. Cosmetic results were excellent/good in 87.8% of patients and fair/poor in 12.2%. Hypofractionated WBRT with concomitant boost to the lumpectomy cavity after BCS in EBC led to consistent clinical results at 10 years. Hence, it can be considered a valid treatment option in this setting.     

A phase Ⅱ trial of comprehensive treatment based on radiotherapy in leptomeningeal metastasis

Objective To evaluate the efficacy and safety of comprehensive treatment based on radiotherapy for patients with leptomeningeal metastases (LM) in this prospective study. Methods A total of 93 patients diagnosed with LM admitted to our hospital undergoing whole brain radiotherapy (WBRT) or craniospinal irradiation (CSI) with or without simultaneous boost from 2014 to 2017 were enrolled. The dynamic changes of clinical signs and symptoms, enhanced magnetic resonance imaging (MRI), cerebrospinal fluid cytology and liquid biopsy detection were recorded. The primary endpoint was overall survival (OS),the secondary endpoints were local control (LC), intracranial progress-free survival (IPFS), brain metastasis specific survival (BMSS) and toxicity. Results The major primary disease was non-small cell lung cancer. The whole cohort received WBRT with boost (40 Gy in 20 fractions (f) for WBRT and 60Gy in 20 f for boost), focal radiation to LM, WBRT and CSI (40 Gy in 20 f or 50Gy in 25 f for WBRT and 36 Gy in 20 f for CSI). For 20 patients, tumor cells were identified and intrathecal chemotherapy was performed. Sixty-three patients received target therapy. The median follow-up time was 33.8 months. The 1-year OS, LC and IPFS was 62.4%, 77.2% and 52.6%, respectively. The median survival time was 15.9 months, and the median BMSS was 42.2 months.Treatment-related grade 3–4 adverse events were rare and only 8 cases was observed to have grade 3 hematological toxicity. Conclusion Reasonable comprehensive treatment including precise radiotherapy, intrathecal chemotherapy and targeted therapy can be well tolerated and prolong the survival time of LM patients.     

放疗为主的综合方案治疗脑膜转移瘤Ⅱ期临床研究

目的 前瞻性分析脑膜转移瘤以放疗为主的综合治疗方案的有效性及安全性。方法 纳入2014-2017年中国医学科学院肿瘤医院收治的93例脑膜转移瘤患者,接受螺旋断层放疗技术实施的全脑放疗、局部推量和/或全脊髓照射为基础的综合治疗,记录临床症状、磁共振检查、脑脊液细胞学、液体活检变化情况及不良反应。主要研究终点为总生存(OS),次要研究终点为局部控制(LC)、颅内无进展生存(IPFS)及脑转移专项生存(BMSS)及不良反应。结果 主要原发病为非小细胞肺癌。全组接受全脑放疗±局部推量(中位剂量分别为40Gy分20次、60Gy分20次)或全脑、全脊髓照射(中位剂量分别为40Gy分20次或50Gy分25次、36Gy分20次)。20例找到肿瘤细胞并行鞘注化疗;63例接受靶向治疗。中位随访时间33.8个月,1年OS、LC及IPFS分别为62%、77%及53%。中位生存时间15.9个月,中位BMSS时间42.2个月。3-4级不良反应少见,仅观察到8例3级血液学不良反应。结论 精准放疗结合鞘注化疗或靶向治疗的综合治疗方法,可有效延长脑膜转移瘤患者的生存时间,且不良反应可耐受。     

Hypofractionated stereotactic radiotherapy in combination with whole brain radiotherapy for brain metastases

BACKGROUND: The efficacy and toxicity of hypofractionated stereotactic radiotherapy (HSRT) in combination with whole brain radiotherapy (WBRT), for the treatment of 1-4 brain metastases, using a non invasive fixation of the skull, was investigated. METHODS: Between 04/2001 and 01/2006 30 patients with 44 brain metastases underwent irradiation. Every patient received WBRT (10 x 3 Gy); 41/44 lesions received HSRT boost with a median dose fraction of 6 Gy, the fractionation schemes were 3 x 6 Gy and 4 x 8 Gy; a median total dose of 18 Gy was delivered to the tumor isocenter. RESULTS: The median survival period was 9.15 months, the actuarial 1-year overall survival and freedom from new brain metastases were 36.6% and 87.9%, respectively; at univariate analysis Karnofsky Performance Status (KPS) was statistically significant (P = 0.05); the actuarial 1-year local control for the 41/44 lesions was 86.1%. No patient had acute or late complications. CONCLUSIONS: HSRT as a concomitant boost during WBRT is a safe and well tolerated treatment for selected patients with brain metastases.     

乳腺癌保乳术后同步加量调强放疗的临床疗效

目的:探讨乳腺癌保乳术后同步加量调强放疗的疗效、不良反应及美容效果。方法:2008年~2010年收治乳腺癌保乳术后患者78例,其中38例行瘤床同步加量调强放疗（A组）,剂量分割方案为全乳50Gy/25次（2Gy/次）,瘤床同步加量至60Gy/25次（2.4Gy/次）,总疗程33~35天;40例行常规分割调强放疗（B组）,剂量分割方案为全乳50Gy/25次,后续瘤床推量10Gy/5次（2Gy/次）,总疗程40~42天。应用Kaplan-Meier法生存分析,Log-rank法检验差异。结果:中位随访时间为73个月,随访率为100%。两组5年总生存率均为100%。A组和B组5年局部无复发生存率、无病生存率分别为97.4%、97.5%（P=0.978）;97.4%、95.0%（P=0.589)。A组和B组1、2级急性皮肤反应发生率分别为57.9%、52.5%(P＝0.632); 13.2%、12.5%(P＝0.931);A组和B组的1级皮肤及皮下组织晚期反应发生率分别为15.8%、15.0%（P=0.932）;1级白细胞减少发生率分别为7.9%、10.0%（P=0.745）。A组和B组在放疗前、放疗后3、5年美容效果优良率分别为86.8%、87.5%（P=0.931）;84.2%、85.0%（P=0.932）;81.6%、82.5%（P=0.916）。结论:保乳术后同步加量调强放疗的疗效与常规分割调强放疗相似,美容效果及不良反应相当。     

Sole brachytherapy of the tumor bed after conservative surgery for T1 breast cancer: five-year results of a phase I-II study and initial findings of a randomized phase III trial

BACKGROUND AND OBJECTIVES: The objectives of this study were to test the feasibility of sole interstitial high-dose-rate brachytherapy (HDR-BT) after breast-conserving surgery (BCS) for T1 breast cancer in a phase I-II study, and to present the initial findings of a phase III trial comparing the efficacy of tumor bed radiotherapy (TBRT) alone with conventional whole breast radiotherapy (WBRT). METHODS: Forty-five prospectively selected patients with T1 breast cancer undergoing BCS were enrolled into a phase I-II study of TBRT alone, using interstitial HDR implants. HDR-BT of 7 x 4.33 Gy (n = 8) and 7 x 5.2 Gy (n = 37) was delivered to the tumor bed. Based on the results of this phase I-II study, a further 126 patients were randomized to receive 50 Gy WBRT (n = 63) or TBRT alone (n = 63); the latter consisted of either 7 x 5.2 Gy HDR-BT (n = 46) or 50-Gy wide-field electron irradiation (n = 17). Breast cancer related events and side effects were assessed. RESULTS: In the phase I-II study, at a median follow-up of 57 months, 2 (4.4%) local, 3 (6.7%) axillary, and 3 (6.7%) distant failures were observed. Two patients (4.4%) died of breast cancer. The 5-year probability of cancer-specific, relapse-free and local recurrence-free survival was 90.0%, 85.9%, and 95.6%, respectively. The cosmetic results were judged to be excellent in 44 of 45 patients (97.8%). Severe (higher than grade 2) skin sequelae or fibrosis was not found. Symptomatic fat necrosis occurred in one patient (2.2%). In the phase III study, at a median follow-up of 30 months, the locoregional tumor control was 100% in both arms. The 3-year probability of cancer-specific and relapse-free survival was 98.1% and 98.4% in the WBRT group and 100% and 94.4% in the TBRT group, respectively (P = NS). There was no significant difference between the two treatment arms regarding the incidence of radiation side effects. CONCLUSIONS: Five-year results of our phase I-II study prove that sole HDR-BT of the tumor bed with careful patient selection and adequate quality assurance is a feasible alternative to WBRT. However, long-term results of phase III trials are required to determine the equivalence of TBRT alone, compared with WBRT in the management of selected patients with early breast cancer.     

A preliminary report of intraoperative radiotherapy (IORT) in limited-stage breast cancers that are conservatively treated

Local recurrences after breast conserving surgery occur mostly in the quadrant harbouring the primary carcinoma. The main objective of postoperative radiotherapy should be the sterilisation of residual cancer cells in the operative area, while irradiation of the whole breast may be avoided. We have developed a new technique of intra-operative radiotherapy (IORT) of a breast quadrant after the removal of the primary carcinoma. A mobile linear accelerator (linac) with a robotic arm is utilised delivering electron beams able to produce energies from 3 to 9 MeV. Through a perspex applicator, the radiation is delivered directly to the mammary gland and to spare the skin from the radiation, the skin margins are stretched out of the radiation field. To protect the thoracic wall, an aluminium-lead disc is placed between the gland and the pectoralis muscle. Different dose levels were tested from 10 to 21 Gy without important side-effects. We estimated that a single fraction of 21 Gy is equivalent to 60 Gy delivered in 30 fractions at 2 Gy/fraction. Seventeen patients received a dose of IORT of 10 to 15 Gy as an anticipated boost to external radiotherapy, while 86 patients received a dose of 17–19–21 Gy intra-operatively as their whole treatment. The follow-up time of the 101 patients varied from 1 to 17 months (mean follow-up time was 8 months). The IORT treatment was very well accepted by all of our patients, either due to the rapidity of the radiation course in cases where IORT was given as the whole treatment or to the shortening of the subsequent external radiotherapy in cases where IORT was given as an anticipated boost. We believe that single dose IORT after breast resection for small mammary carcinomas may be an excellent alternative to the traditional postoperative radiotherapy. However, a longer follow-up is needed for a better evaluation of the possible late side-effects.     

Hypofractionation with no boost after breast conservation in early-stage breast cancer patients

The aim of this study was to evaluate local control, survival and toxicity profile of a consecutive cohort of early-stage breast cancer (EBC) patients treated with adjuvant hypofractionated radiotherapy (HF) with no boost delivered to the lumpectomy cavity, after breast-conserving surgery (BCS). Between 2005 and 2015, a total of 493 women affected with EBC were treated with HF (46 Gy/20 fractions or 40.05 Gy/15 fractions) to the whole breast without boost to tumor bed, because of age and/or favorable tumor characteristics. The primary endpoint was 5-year actuarial local control (LC); secondary endpoints included survival, toxicity profile and cosmesis. Median follow-up was 57 months (range 6–124). Actuarial 5-year overall, cancer-specific, disease-free survival and LC were 96.3, 98.9, 97.8 and 98.6 %, respectively. On multivariate analysis, tumor stage (T1 vs. T2) and hormonal status (positive vs. negative estrogen receptors) were significantly correlated with LC. Only 2 % of patients experienced ≥G3 acute skin toxicity. Late toxicity was mild with only 1 case of G3 fibrosis. Most of the patients (95 %) had good–excellent cosmetic results. HF to the whole breast with no boost delivered to the tumor bed is a safe and effective option for a population of low-risk breast cancer patients after BCS, with excellent 5-year LC, mild toxicity profile and promising cosmetic outcome. A subgroup of patients with larger tumors and/or with no estrogen receptor expression may potentially benefit from treatment intensification with a boost dose to the lumpectomy cavity.     

早期乳腺癌保乳术后全乳IMRT及瘤床大分割同期加量的临床Ⅱ期研究

目的 早期乳腺癌保乳术后全乳IMRT及瘤床大分割同期加量的临床Ⅱ期研究。方法
2010—2013年本中心前瞻性收治200例早期乳腺癌保乳术患者,采用IMRT全乳45 Gy分25次同期瘤床加量0.6 Gy/次总量60 Gy5周完成方案。Logistic 回归分析用于检验发生2级放射性皮肤反应的预测因素。     

乳腺癌保留乳房术后大分割调强放疗初步临床观察

目的：观察早期乳腺癌保留乳房术后三维适形放疗（three-dimensional conformal radiotherapy,3-DCRT）、常规分割调强放疗（intensity-modulated radiotherapy,IMRT）及大分割调强放疗（hypo-fractionated intensity-modulated radiotherapy,hIMRT）的疗效、不良反应及美容效果。方法：选择2009～02—01—2013-01—31潍坊市人民医院放疗科早期乳腺癌保留乳房术后女性患者66例,根据患者意愿分别纳入3-DCRT、IMRT或kIMRT组行放疗。3DCRT组采用6Mv_X射线切线野照射,全乳腺Dr50Gy／25次,2Gy／次,后续9／12MeV电子线予瘤床区补量10Gy／5次,2Gy／次;IMRT组：采用逆向动态调强技术,以切线野方向为调强主野的入射方向,全乳腺50Gy／25次,2Gy／次,瘤床区用X射线同步加量至60Gy／25次,2．4Gy／次,或全乳腺放疗结束后行电子线补量（方式及剂量同3DCRT）;h-IMRT组：全乳腺42．5Gy／16次,2．66Gy／次,瘤床区同步X射线加量至48Gy。结果：3-DCRT组、IMRT组、h_IMRT组分别入组46、12和8例,中位随访23．9个月（2．1～48．0个月）,3组患者免疫组化结果、病理类型、TNM分期、放化疗顺序及化疗方案、年龄、手术与术后’放疗时间间隔、肿瘤最大径和腋窝淋巴结转移数目差异均无统计学意义,P〉0．05;3组放疗时间差异有统计学意义,P〈O．01,其中h-IMRT组周期最短。单变量一般线性模型三因素方差分析显示,放疗前后乳头纵向、横向位置,乳房横径,乳根位置差异均无统计学意义,P〉O．05;保留乳房术后患者健侧乳头比患侧低,P〈0．05;3组间乳头横向位置和乳房横径差异有统计学意义,P〈O．05。3组患者均发生不同程度的急性血液系统和皮肤反应,但差异无统计学意义,P〉0．05,无Ⅲ度及更严重的急性放射性皮肤反应,均未影响放疗计划的顺利进行。结论：短期随访结果显示,早期乳腺癌保留乳房术后大分割调强放疗组可以明显缩短放疗时间,未加重血液系统及皮肤急性毒副作用,未增加局部复发风险,未降低总生存,未降低美容效果,很有可能成为中国女性早期乳腺癌保留乳房术后安全有效的放疗模式。     

Hypofractionated conformal stereotactic radiotherapy alone or in combination with whole-brain radiotherapy in patients with cerebral metastases

PURPOSE: The aim was to evaluate treatment of cerebral metastases with hypofractionated conformal stereotactic radiotherapy (HCSRT) or whole-brain radiotherapy (WBRT) in combination with a stereotactic boost. METHODS AND MATERIALS: Forty-seven patients were treated with HCSRT and 14 patients with WBRT in combination with a stereotactic boost. Radiation doses were 40 Gy (5 fractions) in HCSRT or 30 Gy (WBRT) combined with a mean dose of 17 Gy stereotactically (1-3 fractions). RESULTS: The median survival time in the HCSRT as well as the WBRT group was 5.0 months, and 87% died of extracranial disease. Radiologic follow-up (mean, 3.7 months after treatment) showed local control in the HCSRT group in 84% and in the WBRT group in 100%. Patients treated with HCSRT developed new brain metastases distant from the irradiated area in 25%. Two patients treated with HCSRT deteriorated neurologically during treatment, and in 2 patients radionecrosis developed. CONCLUSIONS: Although there may be a higher risk of distant new metastases, HCSRT as a treatment for brain metastases seems to be as effective as WBRT in combination with a stereotactic boost. Complications are in the range of what has been reported previously.     

Comparison of Two Radiotherapeutic Hypofractionated Schedules in the Application of Tumor Bed Boost

AimEvaluation of related radiation toxicity and efficacy in terms of local control of 2 radiotherapeutic hypofractionated schedules in the application of tumor bed boost by using 2 different planning techniques.MethodEighty-one patients with stage I-II disease were retrospectively selected with either concomitant (group A) or sequential (group B) boost for the tumor bed. In group A, 27 patients were treated with a total dose of 46 Gy to the whole breast and 54 Gy to the tumor bed in 20 concomitant fractions. In group B, 54 patients were treated with a total dose of 42.4 Gy in 16 fractions to the whole breast and 53 Gy to the tumor bed by 4 sequential fractions. The boost was administered with multiple photon-beam fields. The median follow-up time was 24 months.ResultsThe statistical analysis for the 2 groups of the study showed that skin toxicity was significantly worse in group A (P < .05, Kruskal-Wallis H test). For groups A and B at the completion of radiation therapy, grade 1 skin toxicity was observed in 18/27 patients (66.6%) and 13/54 patients (24.1%), respectively, whereas grade 2/3 was observed in 9/27 patients (33.3%) vs. 5/54 patients (9.3%), respectively (P < .001). One year after irradiation, in group A and in group B, the skin toxicity was of grade 1 in 6/27 patients (22.2%) vs. 2/54 patients (3.7%), respectively (P = .008). Within 2 years, the breast returned to its original form in all patients. No patient showed local disease recurrence.ConclusionsThe accelerated hypofractionated schedules in the application of the tumor bed boost by using the 2 different planning techniques appears to be effective and well tolerated.