Contrast ultrasound-guided photothermal therapy using gold nanoshelled microcapsules in breast cancer

Objectives

The purpose of this study was to test whether dual functional gold nano-shelled microcapsules (GNS-MCs) can be used as an ultrasound imaging enhancer and as an optical absorber for photothermal therapy (PTT) in a rodent model of breast cancer.

Methods

GNS-MCs were fabricated with an inner air and outer gold nanoshell spherical structure. Photothermal cytotoxicity of GNS-MCs was tested with BT474 cancer cells in vitro and non-obese diabetes-SCID (NOD/SCID) mice with breast cancer. GNS-MCs were injected into the tumor under ultrasound guidance and treated with near-infrared (NIR) laser irradiation. The photothermal ablative effectiveness of GNS-MCs was evaluated by measuring the surface and internal temperature of the tumor as well as the size of the tumor using histological confirmation.

Results

NIR laser irradiation resulted in significant tumor cell death in GNS-MCs-treated BT474 cells in vitro. GNS-MCs were able to serve as an ultrasound enhancer to guide the intratumoral injection of GNS-MCs and ensure their uniform distribution. In vivo studies revealed that NIR laser irradiation increased the intratumoral temperature to nearly 70 °C for 8 min in GNS-MCs-treated mice. Tumor volumes decreased gradually and tumors were completely ablated in 6 out of 7 mice treated with GNS-MCs and laser irradiation by 17 days after treatment.

Conclusion

This study demonstrates that ultrasound-guided PTT with theranostic GNS-MCs is a promising technique for in situ treatment of breast cancer.     

Polylactide nanoparticles encapsulating indocyanine green for photothermal therapy of prostate cancer cells

BackgroundThe aim of this study is to investigate the in vitro phototherapeutic potential of indocyanine green (ICG) loaded polylactide (PLA) nanoparticles on prostate cancer cells. Many attempts at designing drug delivery systems against cancer were made that incorporates ICG as a photothermal, photodynamic or imaging agent. However, most of these systems contain at least one more drug, making it hard to assess the effects of ICG alone.MethodsNanoparticles (ICGNP) were prepared via nanoprecipitation. The effects of phase volume ratio and ICG concentration on size, loading capacity and encapsulation efficiency were explored. Photothermal and photodynamic properties of ICGNP were examined. PC-3 cells were used for cell viability tests. Irradiation was achieved via custom built 809-nm computer controlled diode laser at 1 W/cm² (up to 600 J/cm²). Data were analyzed by ANOVA followed by Tukey's test (p ≤ 0.05).ResultsICGNP exhibited mean size of 300 nm with low polydispersity, and zeta potential of -14 mV. Upon laser irradiation, ICGNP were capable of causing temperature increase and producing singlet oxygen. On PC-3 cells, ICGNP were proved to be as effective as free ICG in inducing cell death. The measured temperature increase in culture medium and experiments with singlet oxygen quenchers suggest that the decrease in cell viability was mainly the result of photothermal action.ConclusionsICGNP was effective as a photothermal agent on PC-3 cells but further improvements are required to increase ICG loading capacity for it to be useful on a wide range of cell types.     

Gold nanoparticles as novel agents for cancer therapy

Gold nanoparticles are emerging as promising agents for cancer therapy and are being investigated as drug carriers, photothermal agents, contrast agents and radiosensitisers. This review introduces the field of nanotechnology with a focus on recent gold nanoparticle research which has led to early-phase clinical trials. In particular, the pre-clinical evidence for gold nanoparticles as sensitisers with ionising radiation in vitro and in vivo at kilovoltage and megavoltage energies is discussed.     

Mammography after conservative therapy for breast cancer

One hundred and seventy-five patients who received conservative therapy for breast cancer were followed regularly by mammography. Localised changes due to limited surgery, as well as more generalised changes caused by irradiation, demonstrated a chronological course during the follow-up. This course was uncomplicated in 75% of our patients. Of the cases, 18% were complicated by an incomplete primary biopsy, a contralateral carcinoma, peripheral metastases or a cancer-related death. In the remaining 7%, an intramammary recurrence occurred ipsilaterally. More than half of these recurrences were diagnosed within 2 years after therapy, and therefore were probably caused by inadequate therapy of the primary cancer. Correspondence to: M. Kessler     

Role of irradiation in breast conservation therapy for breast cancer

Despite a worldwide consensus on the indication for breast conservation therapy (BCT), the proportion of patients treated with BCT in Japan was only 29.2% in 1997. Indications of BCT and opinions against increasing the number of BCT in Japan are discussed along with the concept of evidence-based medicine (EBM). It is evident that in Japan as well, 70% to 90% of patients with breast cancer can be treated with BCT. The main aim of irradiation in BCT is to reduce inbreast recurrences (IBR), and randomized controlled trials have confirmed that irradiation to the breast reduces IBR. Currently, much concern is being directed to the issue of surgical margins in partial mastectomy, i.e., the definition of positivity of margins and how to treat margin-positive cases. The role of boost irradiation to the tumor bed and irradiation to lymph node areas are also discussed.     

乳腺癌保乳治疗后的X线随访

目的分析乳腺癌保乳治疗后X线征象的变化规律。方法搜集1999至2005年3月行保乳治疗，并有完整随访资料的85例，总随访次数139例次，随访时间为前2年每6个月1次，以后则1年1次。在不同的术后时间段观察乳腺X线改变，重点观察水肿、皮肤增厚、结构紊乱、局限性致密、结构扭曲收缩、钙化等。各种X线征象随时间而发生的变化用多个独立样本非参数检验的Kruskal-Wallis H检验法，在不同时间段中某一征象出现的频数以及不同征象与乳腺腺体分型间的关系用χ^2检验。随访时间从手术后1周至72个月。结果2例（1．4％）未见阳性X线征象。术后12和24个月这2个时间段随访X线征象阳性率较高，为40．3％（56／139）和21．6％（30／139）。保乳治疗后在不同时间段出现的征象不同（χ^2=30．998，v=6，P=0．001）。手术后水肿程度各异，峰值出现在手术后6个月至1年左右，随后逐步消退、消失；皮肤增厚的出现和消退呈与水肿相似的发展过程。结构紊乱出现和消失与时间无明显相关性（χ^2=8．634，P〉0．05），但结构紊乱程度可随时间而改善（17／19）。不对称性致密仅见5例，3例在后期消失。结构扭曲收缩随时间的延长而明显，并在一定时间后保持恒定。2例显示钙化，为肿瘤残留和缝线钙化各1例。结论乳腺癌保乳治疗后在不同的时间段X线征象改变不同，了解其改变的规律是鉴别可能出现复发的基础。     

Organizing pneumonia after radiation therapy for breast cancer

We report a case of organizing pneumonia (OP) that developed after radiation therapy (RT) for breast cancer. A 54-year-old woman presented with malaise and fever within a month after the completion of RT for breast cancer. Chest radiographs and computed tomography (CT) demonstrated consolidation in the left upper lobe consistent with radiation pneumonia. The patient was given 60 mg/day IV cortisone for 15 days after which her complaints and consolidation in the left upper lobe disappeared. The daily dose of her corticosteroid was tapered down to 20 mg/day. Two weeks later, the patient again had fever and malaise. Chest X-ray and CT revealed bilateral pulmonary opacities located outside the irradiated fields, predominantly in the middle and lower lung zones. The patient's laboratory tests were normal except for her erythrocyte sedimentation rate, which was elevated. Bronchial lavage revealed moderate elevation of the total cell number with lymphocyte predominance. Open lung biopsy was performed and histopathological examination demonstrated findings consistent with OP. High dose (60 mg/day) prednisolone treatment resulted in rapid clinical and radiological improvement. When the prednisolone dose was gradually tapered down to 20 mg/day during follow-up, new pulmonary opacities developed in both lungs, as well as the recurrence of the patient's symptoms. Increased dose of prednisolone resulted in the rapid improvement of the clinical symptoms and radiological abnormalities. OP rarely presents after RT for breast and lung cancer. One should always consider OP in the clinical setting of a patient who has a history of RT completed 3-6 months prior to fever, multiple areas of consolidation, and ground glass opacities outside the RT field.     

Long-term outcome of breast-conserving therapy for breast cancer

PURPOSE: We present a retrospective analysis of long-term therapeutic results for patients treated in our institution to evaluate the efficacy of breast-conserving therapy (BCT). PATIENTS AND METHODS: The study population was 99 patients (102 breasts) with stage 0, I, and II breast cancer who underwent breast conservation therapy between April 1990 and November 1997. The entire breast was irradiated to a median dose of 50 Gy (range, 50-60 Gy) in 25-30 fractions. An additional 10 Gy in five fractions with 6-12 MeV electrons was given to 23 breasts (23%) with positive surgical margins. RESULTS: The 5-/10-year overall survival, cause-specific survival, relapse-free rate, local recurrence, and regional recurrence rates were 94.6/93.3%, 95.7/94.5%, 88.2/77.5%, 4.2/8.5%, and 2.0/6.3%, respectively. In both uni- and multivariate analyses, age < 40 years was a significant prognostic factor for local recurrence. No severe morbidity was observed. CONCLUSION: The long-term clinical outcome of BCT for early breast carcinoma patients in our department was favorable. Patient age <40 was the most important factor associated with an increased risk of local recurrence in the ipsilateral breast.     

Monitoring therapy in breast cancer

Breast cancer remains one of the most common cancers in the developed world. New treatments are proving effective against both limited disease and metastases. Nuclear medicine is in a unique position as it is one of the only methods used to image the breast which is linked to cell cycle changes, the receptors on the cell surface and the cells' response to chemotherapy. Nuclear medicine is unaffected by the anatomical changes seen post-chemotherapy and radiotherapy and is uniquely placed to become a major methodology in the continued assessment of the breast cancer patient. However, before this can happen the utility of nuclear medicine techniques must be proved in multi-centre trials.     

乳腺癌保乳治疗304例的临床分析

目的 探讨Ⅰ～Ⅱ期乳腺癌保乳治疗的临床效果及存活率和局部复发的影响因素.方法 收集1988年6月～2005年6月在解放军总医院住院的304例临床Ⅰ～Ⅱ期乳腺癌患者,所选患者均行乳腺肿瘤局部切除,腋窝淋巴结清扫及术后放疗.所有患者接受了术后化疗,雌激素受体阳性者口服三苯氧胺.中位随访时间8.1年.结果 患者5年总存活率,疾病特异性存活率及无局部复发存活率分别为92.58%,93.46%,86.26%.10年总存活率,疾病特异性存活率及无局部复发存活率分别为85.29%,88.27%,77.75%.5年和10年的局部复发率分别为5.5%和11.7%.统计结果 显示,年龄(＜40岁),腋窝转移淋巴结数量(＞4)与疾病特异性存活率相关联;而年龄(＜40岁),雌激素受体阴性与局部复发相关联.24例局部复发者均切除了同侧乳腺,随访5～130个月,有5例死亡.并发症为30例次.结论 保乳治疗具有很高的长期存活率,局部控制率和较低的并发症发生,是治疗Ⅰ～Ⅱ期乳腺癌的可靠方法 .     

Photodynamic therapy for chest wall recurrence from breast cancer

Breast cancer is common with over 230,000 new cases diagnosed each year in North America alone. While great strides have been made to achieve excellent cancer control and survival, a significant minority of patients fail locally. While initial salvage to regain disease control is of the utmost importance, it is not universally successful. This leads to a therapeutic quagmire. Additional surgery, radiation and chemo-hormonal therapy are possible, but they are usually highly morbid with low success rates. Photodynamic therapy appears to be an underutilized salvage modality for this unfortunate patient population. This report analyzes and reviews the role of photodynamic therapy for patients with chest wall re-recurrence from breast cancer.     

Radioimmunodetection and therapy of breast cancer

Breast cancer is the second most-common cause of cancer death in women in the United States. Although more than 60% of patients can now be cured by initial treatment, the rest, although perhaps receiving palliation with currently available therapy, will die of their disease. Early detection of micrometastasis and improved treatment strategies are needed. Monoclonal antibody (mAb)-based imaging and tumor targeted therapy holds the potential to impact these problems. The most significant results of systemically administered antibody-based radiopharmaceuticals for detection and targeted therapy (radioimmunotherapy [RIT]) of breast cancer give strong evidence that this potential can be realized. Interest in immunoimaging recently has focused on small mAb modules used with 18F, 64Cu, or 124I to detect minimal disease in breast cancer by positron emission tomography or single-photon emission computed tomography. Reported therapy trials in advanced breast cancer have yielded objective responses and minimal toxicity. These studies have spanned several radionuclides as well as several mAb, fragments and approaches, including dose intensification with bone marrow support; combined therapy with other modalities (ie, CM-RIT); biodegradable peptide linkers; and pretargeting. RIT evaluated in clinical breast cancer trials has delivered as much as 4000 cGy to metastatic breast cancer per therapy dose with marrow stem cell support. Preclinical studies have demonstrated further promising strategies for breast cancer. RIT studies must address the key issue: enhancing the therapeutic index (tumor effect verses most sensitive normal tissue (bone marrow) effect). Approaches now include newly engineered mAb, scFv modular constructs, blood clearance on demand, enhanced pretargeting, applications of both alpha and beta emitting radionuclides, and combination therapy using molecular triggers for therapeutic synergy. These strategies for detection and treatment of metastatic breast cancer should lead to notable clinical impact on management and cure of breast cancer.     

Abnormalities on chest radiographs following radiation therapy for breast cancer

The aim of this study was to study pulmonary radiological abnormalities with chest radiography following different radiotherapy (RT) techniques for breast cancer with respect to regions and density, and their association with pulmonary complications and reduction in vital capacity (VC). Chest radiographs were performed 5 months following local or loco-regional RT in 167 breast cancer patients. The radiological abnormalities were analysed with a classification system originally proposed by Arriagada and evaluated according to increasing density (0–3) and affected lung regions (apical–lateral, basal–lateral, central–parahilar). The highest-density grades in each region were added together to form scores ranging from 0 to 9. The patients were monitored for RT-induced pulmonary complications. The VC was measured prior to and 5 months following RT. An independent evaluation of 51 patients was performed by a second radiologist to control the reproducibility of the classification system. Increasing scores were associated with loco-regional RT and pulmonary complications (P < 0.001). The mean reduction of VC for patients scoring 0–3 (–30 ml) vs 4–9 (–161 ml) was not statistically significant (P = 0.10). Scores of 4–9 were more frequently observed in older patients (P < 0.001). The independent evaluations by two radiologists revealed good agreement (P < 0.001) and no systematic inter-observer variation. Radiological abnormalities on chest radiographs, scored according to Arriagada, can be used as an objective end point for RT-induced pulmonary side effects in breast cancer. Received: 4 February 1999; Revision received: 1 April 1999; Accepted: 5 May 1999     

乳腺癌介入治疗指南的建议

动脉灌注化疗栓塞是治疗局部进展期乳腺癌的一种方法,主要目的 是获得局部手术切除的机会和控制临床症状,该方法已应用于临床并获得了较好的治疗效果.本文根据国内外已发表的乳腺癌介入治疗相关文献,主要从乳腺癌血液供应、造影表现、介入治疗的术前准备、适应证、禁忌证、用药、并发症防治及治疗效果等方面进行归纳总结,为制订乳腺癌介入治疗的指南提供一些参考.     

Therapeutic potential of melatonin for breast cancer radiation therapy patients

Melatonin is an endogenous hormone primarily known for its action on the circadian rhythms. But pre-clinical studies are reporting both its radioprotective and radiosensitizing properties, possibly mediated through an interaction between melatonin and the regulation of estrogens. Melatonin pre-treatment prior to ionizing radiation was associated with a decrease in cell proliferation and an increase in p53 mRNA expression, leading to an increase in the radiosensitivity of breast cancer cells. At the same time, a decrease in radiation-induced side effects was described in breast cancer patients and in rodent models. This review examines the potential for melatonin to improve the therapeutic outcomes of breast radiation therapy, specifically estrogen receptor positive patients. Evidence suggests that melatonin may offer a novel, non-toxic and cheap adjuvant therapy to improve the existing treatment modalities. But further research is required in the clinical setting before a clear understanding of its therapeutic benefits is determined.     

Risk analysis of electronic intraoperative radiation therapy for breast cancer

PurposeTo evaluate the process and improve safety of intraoperative radiation therapy (IORT) for early-stage breast cancers treated with electronic brachytherapy.Methods and MaterialsA multidisciplinary team conducted a failure mode and effects analysis (FMEA) for IORT breast cancer treatments by first developing a process map. This map was then used to identify failure modes for all steps in the treatment workflow. Risk priority numbers (RPNs) were assigned to each failure mode and were calculated as the product of the failure mode's probability of occurrence (O), severity (S), and lack of detectability (D). Corrective steps were implemented to address failure modes with the highest risk, and a revised process was generated.ResultsThe steps with the highest risk failure modes were related to source calibration, use of correct plan and dwell times, and the correct site and intent. The introduction of a physician calibration check and an extended time-out checklist reduced the risk of these failure modes. The highest risk steps in the Xoft breast IORT treatment process are associated with source calibration and manual entry of dwell positions for each balloon size and volume combination. High-risk failure modes that could be mitigated with improved hardware and software interlocks were identified.ConclusionHigh-risk failure modes are identified with FMEA and addressed with corrective steps. This application of FMEA can be used in principle for clinical processes throughout breast cancer care. This analysis demonstrates the importance of well-designed QC policies, procedures, and oversight in a Xoft electronic brachytherapy program for breast cancer IORT.     

Mammographic appearance of recurrent breast cancer after breast conservation therapy

RATIONALE AND OBJECTIVES: To compare the mammographic appearance of recurrent breast cancer to the primary tumor in patients treated with breast conservation therapy. MATERIALS AND METHODS: The charts of women with American Joint Committee on Cancer Stage I or II breast cancer who underwent breast conservation therapy between 1977 and 2001 at our institution were reviewed. A total of 132 patients were diagnosed with local recurrence. RESULTS: The mammographic appearance of the local recurrence often varied from the appearance of the original breast cancer. This was especially true for women who had mammographically occult primary breast cancer. In these women, the recurrence was detected mammographically 76.9% of the time. CONCLUSIONS: Given the variable appearance of the local recurrence after breast conservation therapy, any suspicious finding needs to be carefully evaluated regardless of the mammographic appearance of the original tumor.