Nodal Response to Neoadjuvant Chemotherapy Predicts Receipt of Radiation Therapy After Breast Cancer Diagnosis.

BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is associated with improved overall survival (OS) in patients with breast cancer, but it is unclear how post-NACT response influences radiation therapy administration in patients presenting with node-positive disease. We sought to determine whether nodal pCR is associated with likelihood of receiving nodal radiation and whether radiation therapy among patients experiencing nodal pCR is associated with improved OS. METHODS AND MATERIALS: Clinical N1 (cN1) female breast cancer patients diagnosed during 2010 to 2015 who were ypN0 (ie, nodal pCR; n = 12,341) or ypN1 (ie, residual disease; n = 13,668) after NACT were identified in the National Cancer Database. Multivariate logistic regression was used to identify factors associated with receiving radiation therapy. Cox proportional hazards modeling was used to estimate the association between radiation therapy and adjusted OS. RESULTS: The study included 26,009 patients; 43.9% (n = 5423) of ypN0 and 55.3% (n = 7556) of ypN1 patients received nodal radiation. Rates of nodal radiation remained the same over time among ypN0 patients (trend test, P = .29) but increased among ypN1 patients from 49% in 2010 to 59% in 2015 (trend test, P < .001). After adjusting for covariates, nodal pCR (vs no stage change) was associated with decreased likelihood of nodal radiation after mastectomy (∼20% decrease) and lumpectomy (∼30% decrease; both P < .01). After mastectomy, nodal (vs no) radiation conferred no significant survival benefit in ypN0 patients, but it approached significance for ypN1 patients (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.69-0.99, P = .04; overall P = .11). After lumpectomy, nodal radiation was associated with improved adjusted OS for ypN0 (HR, 0.38; 95% CI, 0.22-0.66) and ypN1 patients (HR, 0.44; 95% CI, 0.30-0.66; both P < .001), but this improvement was not significantly greater than that associated with breast-only radiation. CONCLUSIONS: ypN0 patients were less likely to receive nodal radiation than ypN1 patients were, suggesting that selective omission already occurs and, in the context of limited survival data, could potentially be appropriate for select patients.

The Evolving and Multidisciplinary Considerations in Nodal Radiation in Breast Cancer.

The therapeutic management of regional lymph nodes in breast cancer has seen a remarkable change in the past 2 decades. Clinical trials have refined our knowledge regarding the biology of the disease including the prognostic significance of disease in the regional lymph nodes. The contemporary management of lymph nodes is also influenced by advances in surgical technique, radiation oncology delivery systems, and effective systemic therapy regimens. This paper describes the role of regional nodal irradiation in the context of the de-escalation of axillary surgery, improved understanding of the molecular and pathologic features, and increasing use of neoadjuvant chemotherapy.

Irradiación de áreas ganglionares en pacientes sin linfadenectomía axilar / Axillary radiation in patients without axillary lymphadenectomy

La biopsia selectiva del ganglio centinela (BSGC) es actualmente una propuesta estándar para la estadificación de la axila en pacientes con cáncer de mama con una clara tendencia a minimizar la cirugía axilar incluso en presencia de ganglio centinela (GC) positivo. En caso de GC negativo la BSGC ha reemplazado a la linfadenectomía axilar (LA) demostrando equivalente supervivencia, mientras que los más sólidos consensos (American Society of Clinical Oncology) y, hasta fechas recientes, las guías de la National Comprehensive Cancer Network recomendaban completar la LA cuando se identifican metástasis en el GC. Esto da como resultado un excelente control locorregional y proporciona información que permite tomar decisiones sobre tratamientos adyuvantes tanto al oncólogo médico como al oncólogo radioterápico. No obstante, en los últimos tiempos múltiples estudios han debatido el valor terapéutico de la linfadenectomía quirúrgica, cobrando especial relevancia a raíz de la publicación del ensayo del American College of Surgeons Oncology Group (ACOSOG) Z0011, en el que se cuestiona el valor de esta actitud terapéutica y se propone únicamente una BSGC, omitiéndose la LA, en pacientes seleccionadas con uno o 2 GC positivos. La evidencia científica nos dice que la radioterapia puede jugar un papel fundamental en el control de la enfermedad axilar y, a fecha de hoy, no sabemos si la baja tasa de recidiva a este nivel, en los estudios mencionados, puede estar influida por la irradiación de la mama y axila inferior. Serían necesarios estudios con un diseño apropiado para contestar esta pregunta. En ausencia de más datos, nuestra propuesta es la irradiación axilar valorando individualmente los factores de riesgo de recidiva locorregional(AU)

Sentinel lymph node biopsy (SLNB) is currently a standard approach for staging of the axilla in patients with breast cancer, with a clear tendency to minimize surgery even in the presence of a positive axillary sentinel lymph node (SLN). The strongest consensus (American Society of Clinical Oncology) and, until recently, the National Comprehensive Cancer Network guidelines used to recommend complete axillary lymphadenectomy when metastases were identified in the SLN. However, SLNB has replaced axillary lymphadenectomy in SLN-negative patients and has demonstrated equivalent survival. This approach results in excellent locoregional control and provides information that allows both the medical oncologist and the radiation oncologist to take decisions about adjuvant treatments. Many recent studies, however, have debated the therapeutic value of surgical lymphadenectomy. This debate has become particularly important after the publication of the trial of the American College of Surgeons Oncology Group (ACOSOG) Z0011, which questions the value of this therapeutic approach and proposes SLNB alone, without lymphadenectomy, in selected patients with one or 2 positive SLN. The scientific evidence indicates that radiotherapy may play a major role in the control of axillary disease and, to date, it is not known whether the low recurrence rate in the axilla reported in the above-mentioned studies may have been influenced by radiation of the breast and lower axilla. To answer this question, new and appropriately designed trials are needed. In the absence of more data, we propose the use of axillary radiation, but with assessment of the risk factors for locoregional recurrence in each patient(AU)

Should decisions on internal mammary lymph node irradiation be based on current lymphoscintigraphy techniques for sentinel lymph node identification?

BACKGROUND: Treatment of internal mammary lymph node (IMN) metastases remains controversial because of the difficulty in predicting involvement, potential treatment-related morbidity, and questionable efficacy. Lymphoscintigraphy with sentinel lymph node biopsy offers a means to identify occult involvement of IMN, allowing appropriate patient selection for IMN treatment. METHODS: The authors retrospectively reviewed 262 lymphoscintigraphies (LS) of 248 patients treated at the University of Florida (Gainesville, FL) between 1998 and 2002. Tumor characteristics were assessed for their value in predicting IMN drainage and their association with IMN radiation. RESULTS: Lymph flow to the IMN was documented with LS in 23 of 262 tumor specimens (9%). Flow to the IMN was not correlated with any of the five factors: tumor location, tumor size, lymphovascular invasion, pathologic lymph node status, and laterality of the involved breast (right vs. left breast). Identification of IMN flow increased from 5.7% to 10.1% with the use of a deep injection technique. IMN radiotherapy was used more frequently in patients with larger tumors (15 of 188 in Tis/T1 vs. 31 of 70 in T2-T4; P<0.0001) and positive lymph nodes (17 of 91 in lymph node-negative patients vs. 28 of 66 in lymph node-positive patients; P<0.0001). In patients with T2N0 tumors (n=32), IMN radiotherapy was used more frequently with medial tumors (5 of 11 [45%]) than with lateral tumors (4 of 21 [19%]). CONCLUSIONS: The incidence of flow to the IMN documented with the current LS technique was low compared with other LS and extended radical mastectomy series. Histopathologic information was obtained for the sentinel IMN when IMN flow was identified on the LS. In the absence of histopathologic information, treatment decisions should continue to be based on clinical factors known to be correlated with occult IMN involvement.

Radiotherapy in the curative treatment of breast cancer: current status and future trends. An opinion sample of radiation oncologists active in breast cancer research.

A questionnaire regarding the current practice of breast cancer radiotherapy and possible future trends in this field was filled out by 13 radiation oncologists active in breast cancer research. In the opinion of this small group, radiotherapy is presently included in the initial treatment of the large majority of early breast cancers, particularly in the framework of breast-conserving therapy, which is currently used in > 50% of these patients. Indications for post-mastectomy irradiation vary greatly among respondents, as do attitudes toward the potentially negative aspects of adjuvant radiotherapy. Most respondents feel that their future practices will be significantly influenced by an increase in screen-detected cancers, the aging of the population, the increasing influence of medical oncologists, participation in clinical trials, and increased patient participation in treatment decisions. An increase is foreseen in the use of breast-conserving approaches, radiotherapy, and systemic therapies, and a decrease in the use of both total mastectomy and axillary dissection. Most respondents feel that there will be a modest decrease in the percentage of conservatively operated patients receiving radiotherapy. A future role is seen for neo-adjuvant chemotherapy, at least in well-defined subgroups, increasing the number of patients offered breast-conserving approaches. Most respondents expect that irradiation of lymph nodal areas will gain new credibility and be used more often. No majority opinion could be elicited regarding ways of improving the therapeutic ratio in breast cancer radiotherapy.