Irradiación parcial acelerada de mama (apbi) después de cuadrantectomía más biopsia del ganglio centinela axilar: características clínico-patológicas e inmunohistoquímicas / Accelerated partial breast irradiation (apbi) after breast conservative surgery plus sentinel node biopsy: clinical-pathological and immunohistochemical characteristics

Introducción El tratamiento estándar en estadios tempranos del cáncer de mama es la cirugía conservadora (cc) más radioterapia del volumen total mamario (wbi). Dado que la mayoría de las recidivas locales ocurren cercanas al sitio del tumor (85%) y existiendo la posibilidad de acortar tiempos de irradiación ­debido a que esta insume varias semanas­, podría no ser necesario irradiar toda la mama, sino el área donde estaba situado el tumor más margen de seguridad, lo que insume un menor tiempo. Este el fundamento de la Irradiación Parcial Acelerada Mama (apbi). Consensos internacionales proporcionan guías para administrar apbi fuera de ensayos clínicos. Objetivos El objetivo principal de este trabajo es determinar y analizar las características clinico-anatomopatológicas e inmunohistoquímicas de las pacientes que fueron operadas y luego seleccionadas para ser irradiadas con técnica de apbi con radioterapia externa con intensidad modulada guiada por imágenes (imrt). Material y método Se trata de un trabajo prospectivo, no randomizado. La muestra está constituida por las primeras 20 pacientes ingresadas al protocolo apbi. El reclutamiento se realizó entre marzo de 2012 y julio de 2014. Se analizaron las características clínico-patológicas e inmunohistoquímicas de esas pacientes luego de cc más biopsia del ganglio centinela (bgc). Resultados Media de seguimiento en meses: 37,7 (r: 22-51); edad media: 65,7 años. Tamaño tumoral medio por anatomía patológica: 12,03 mm. Media de número de ganglios centinelas extirpados: 1,7. Todos los tumores fueron unifocales. Los márgenes quirúrgicos resultaron negativos en todos los casos. Tumores Luminal A: 19 pacientes; tumores Luminal B: 1 paciente. Hormonoterapia adyuvante en todas las pacientes. Control locorregional: 100%. Conclusiones A pesar del corto tiempo de seguimiento y del escaso número de pacientes, este análisis sugiere que la apbi en el lecho del tumor marcado intraoperatoriamente con fiduciales de titanio es factible para pacientes que reúnen los criterios estrictos clínico-patológicos e inmunohistoquímicos acordes con las guías internacionales.

Introduction The standard conservative treatment for early stage breast carcinomas is the breast conservative surgery plus whole breast irradiation. Because most local recurrences occur close to the site of the primary tumor (80- 90%) and the possibility of shortening the irradiation times ­because it takes several weeks­, it may not be necessary to irradiate the entire breast, but the area where the tumor was located plus a margin of safety in less time. This is the basis of Accelerated Partial Irradiation of the Breast Objectives Determination and analysis of clinical-pathological and immunohistochemical characteristics in patients selected for Accelerated Partial Breast Irradiation (apbi) performed by imrt + igrt technique after breast conservative surgery plus sentinel node biopsy. Materials and method A prospective, non-randomized study of the first 20 patients performed apbi strictly following the recommendations of international consensus. It was initiated in March 2012 until July 2014. Clinical-pathological and immunohistochemical characteristics of these patients were analyzed to be selected for apbi, after breast conservative surgery plus sentinel node biopsy. Results Median follow up: 37.7 months (r: 22-51); average age: 65.7 years. Mean tumor size by pathological analysis: 12.03 mm. Mean number of sentinel nodes removed: 1.7. All tumors were unifocal. Negative surgical margins in all cases. Luminal A tumors: 19 patients; Luminal B tumors: 1 patient. Adjuvant hormone therapy in all patients. Loco-regional control: 100%. Conclusions Despite the short time of follow up and the small numbers of patients, this analysis suggests that apbi performed by imrt + igrt technique added to the placement of fiduciary marks at the time of surgery is feasible for highly selected patients who meet the clinical-pathological and immunohistochemical selection criteria according to international guidelines

Concurrent use of aromatase inhibitors and hypofractionated radiation therapy.

AIM: To retrospectively assess the acute and long-term toxicity using aromatase inhibitors (AI) therapy concurrently with hypofractionated radiotherapy (HFRT) in breast cancer patients. METHODS: From November 1999 to October 2007, 66 patients were treated with breast HFRT and concurrent AI. In 63 patients (95.5%), HFRT delivered a total dose of 32.5 Gy to the whole breast within 5 wk (five fractions, one fraction per week). Other fractionations were chosen in three patients for the patients' personal convenience. A subsequent boost to the tumor bed was delivered in 35 patients (53.0%). Acute toxicities were scored according to the Common Toxicity Criteria for Adverse Events v3. Late toxicity was defined as any toxicity occurring more than 6 mo after completion of HFRT and was scored according to the Late Effects Normal Tissue Task Force-Subjective, Objective, Management and Analytic scale. RESULTS: At the end of the HFRT course, 19 patients (28.8%) had no irradiation-related toxicity. Acute grade 1-2 epithelitis was observed in 46 patients (69.7%). One grade 3 toxicity (1.5%) was observed. With a median follow-up of 34 mo (range: 12-94 mo), 31 patients (47%) had no toxicity, and 35 patients (53%) presented with grade 1-2 fibrosis. No grade 3 or greater delayed toxicity was observed. CONCLUSION: We found that AI was well tolerated when given concurrently with HFRT. All toxicities were mild to moderate, and no treatment disruption was necessary. Further prospective assessment is warranted.

Implant breast reconstruction followed by radiotherapy: can helical tomotherapy become a standard irradiation treatment?

To evaluate the benefits and limitations of helical tomotherapy (HT) for loco-regional irradiation of patients after a mastectomy and immediate implant-based reconstruction. Ten breast cancer patients with retropectoral implants were randomly selected for this comparative study. Planning target volumes (PTVs) 1 (the volume between the skin and the implant, plus margin) and 2 (supraclavicular, infraclavicular, and internal mammary nodes, plus margin) were 50 Gy in 25 fractions using a standard technique and HT. The extracted dosimetric data were compared using a 2-tailed Wilcoxon matched-pair signed-rank test. Doses for PTV1 and PTV2 were significantly higher with HT (V95 of 98.91 and 97.91%, respectively) compared with the standard technique (77.46 and 72.91%, respectively). Similarly, the indexes of homogeneity were significantly greater with HT (p = 0.002). HT reduced ipsilateral lung volume that received ≥20 Gy (16.7 vs. 35%), and bilateral lungs (p = 0.01) and neighboring organs received doses that remained well below tolerance levels. The heart volume, which received 25 Gy, was negligible with both techniques. HT can achieve full target coverage while decreasing high doses to the heart and ipsilateral lung. However, the low doses to normal tissue volumes need to be reduced in future studies.

One-step customized transurethral resection of the prostate and permanent implant brachytherapy for selected prostate cancer patients: technically feasible but too toxic.

INTRODUCTION: Patients with prominent median lobe hyperplasia and/or high International Prostate Symptom Score (IPSS) are often contraindicated for prostate brachytherapy, mainly because of the risk of post-implant urinary retention. We evaluated an approach combining in the same operative step a limited transurethral resection (TURP) of the median lobe, immediately followed by permanent implant-free seed brachytherapy. METHODS AND MATERIALS: From January 2007 to November 2008, 22 patients underwent a customized limited TURP of their median lobe immediately before brachytherapy. All patients fulfilled our criteria for permanent implant brachytherapy, but presented with a more or less prominent median lobe and/or a high IPSS. RESULTS: The procedure appeared to be technically feasible, with only 0.3% of migrating seeds, a mean post-implant D90 of 173.4 Gy and a mean post-implant V100 of 96.6%. However, 5 patients (23%) experienced a urinary retention, with two patients having to undergo a complementary post-implant TURP. Moreover, urinary toxicity was more pronounced than in our current experience, with high IPSS at 2 months (mean 19.2) and 6 months (mean 15.8). CONCLUSION: Although technically feasible, with relatively few migrating seeds and satisfactory post-implant dosimetric parameters, one-step TURP and brachytherapy was found to be poorly tolerated, with higher than usual urinary retention and urinary toxicity rates. Considering those results, our group is presently evaluating a two-step procedure, with a customized TURP followed after 4-6 months by brachytherapy.

Improving the definition of tumor bed boost with the use of surgical clips and image registration in breast cancer patients.

PURPOSE: To evaluate the accuracy of a boost technique. METHODS AND MATERIALS: Twenty-two patients underwent tumorectomy with placement of two or more clips in the surgical cavity before breast remodeling. Preoperative and postoperative computed tomography scans, with match-point registration, were performed on all patients. The relationship between the location of the gross tumor volume (GTV), defined on the preoperative scan, and clip clinical target volume (CTV) (clips with a 5-mm margin on the postoperative scan) was then studied, by use of commercial volume analysis software. RESULTS: Of the patients, 4 had two clips, 2 had three clips, 8 had four clips, and 8 had five clips. The median GTV was 1.06 mL (range, 0.2-5.3 mL); clip CTV ranged from 2.4 to 21.5 mL. Volumetric analysis showed that in 7 cases (32%), there was no intersection between the GTV and the clip CTV, with the following distribution: 4 patients with two clips, 1 patient with three clips, 1 patient with four clips, and 1 patient with five clips. The common contoured volume was defined as the percent ratio between the intersection of the GTV and clip CTV and the GTV. It was found to be significantly increased if three or more clips were used vs. only two clips (common contoured volume, 35.45% vs. 0.73%; p = 0.028). Finally, the GTV and clip CTV volume relationship can be presented as follows: 12.5% to 33% overlap in 8 patients (36.4%), 50% to 75% in 5 patients (22.7%), and greater than 90% in 2 patients (9%). CONCLUSIONS: The use of three or more clips during tumorectomy increases the accuracy of tumor bed delineation.

Simultaneous integrated boost in breast conserving treatment of breast cancer: a dosimetric comparison of helical tomotherapy and three-dimensional conformal radiotherapy.

BACKGROUND AND PURPOSE: To evaluate the dosimetry of helical tomotherapy (HT) and three-dimensional conformal radiotherapy (3D-CRT) in breast cancer patients undergoing whole breast radiation with simultaneous integrated boost (SIB) of the tumor bed. MATERIAL AND METHODS: Thirteen patients with breast cancer treated by lumpectomy and requiring whole breast radiotherapy with tumor bed boost were planned using both HT and 3D-CRT using the field-in-field technique. The whole breast and tumor bed were prescribed 50.68 Gy and 64.4 Gy, respectively, in 28 fractions. Dosimetries for both techniques were compared. RESULTS: Coverage of the whole breast was adequate with both techniques (V(95%)=96.22% vs. 96.25%, with HT and 3D-CRT, respectively; p=0.64). Adequate tumor bed coverage was also achieved, although it was significantly lower with HT (V(95%)=97.18% vs. 99.72%; p<0.001). Overdose of the breast volume outside the tumor bed was significantly lower with HT (V(54.23 Gy)=12.47% vs. 30.83%; p<0.001). Ipsilateral lung V(20 Gy) (6.34% vs. 10.17%; p<0.001), V(5 Gy) (16.54% vs. 18.53%; p<0.05) and mean dose (4.05 Gy vs. 6.36 Gy; p<0.001) were significantly lower with HT. In patients with left-sided tumors, heart V(30 Gy) (0.03% vs. 1.14%; p<0.05) and mean dose (1.35 Gy vs. 2.22 Gy; p<0.01) were significantly lower with HT, but not V(5 Gy). Contralateral breast V(5 Gy) (0.27% vs. 0.00%; p<0.01) and maximum dose were significantly increased with HT. CONCLUSIONS: In breast cancer treated with SIB, both HT and 3D-CRT provided adequate target volume coverage and low heart doses. Tumor bed coverage was slightly lower with HT, but HT avoided unnecessary breast overdosage while improving ipsilateral lung dosimetry.

Concurrent capecitabine and whole-brain radiotherapy for treatment of brain metastases in breast cancer patients.

Preclinical data have demonstrated that ionizing radiation acts synergistically with capecitabine. This report retrospectively assessed the use of capecitabine concurrently with whole-brain radiotherapy (WBRT) in patients with brain metastases from breast cancer. From January 2003 to March 2005, five breast cancer patients with brain metastases were referred for WBRT with concurrent capecitabine. Median age was 44 years (range: 38-53). The median dose of capecitabine was 1,000 mg/m(2) twice daily for 14 days (day1-14). Treatment cycles were repeated every 21 days, concurrently with WBRT (30 Gy, 3 Gy per fraction, 5 days per week). Median survival after starting WBRT plus capecitabine was 6.5 months (range 1-34 months). One patient achieved a complete response. Two patients achieved partial response, including one with local control lasting until most recent follow-up. One patient had stable disease. The remaining patient was not assessable for response because of early death. Most commonly reported adverse events were nausea (n = 2) and headache (n = 2), always grade 1. Other toxicities were grade 3 hand/foot syndrome (n = 1), moderate anemia requiring transfusion and dose reduction of capecitabine (n = 1), and grade 1 mucositis (n = 1). Although promising, these preliminary data warrant further assessment of capecitabine-based chemoradiation in brain metastases from breast cancer and need to be further validated in the setting of a clinical trial.