Imaging and Management of Internal Mammary Lymph Nodes.

Internal mammary lymph nodes (IMLNs) account for approximately 10%-40% of the lymphatic drainage of the breast. Internal mammary lymph nodes measuring up to 10 mm are commonly seen on high-risk screening breast MRI examinations in patients without breast cancer and are considered benign if no other suspicious findings are present. Benign IMLNs demonstrate a fatty hilum, lobular or oval shape, and circumscribed margins without evidence of central necrosis, cortical thickening, or loss of fatty hilum. In patients with breast cancer, IMLN involvement can alter clinical stage and treatment planning. The incidence of IMLN metastases detected on US, CT, MRI, and PET-CT ranges from 10%-16%, with MRI and PET-CT demonstrating the highest sensitivities. Although there are no well-defined imaging criteria in the eighth edition of the American Joint Committee on Cancer Staging Manual for Breast Cancer, a long-axis measurement of ≥ 5 mm is suggested as a guideline to differentiate benign versus malignant IMLNs in patients with newly diagnosed breast cancer. Abnormal morphology such as loss of fatty hilum, irregular shape, and rounded appearance (which can be quantified by a short-axis/long-axis length ratio greater than 0.5) also raises suspicion for IMLN metastases. MRI and PET-CT have good sensitivity and specificity for the detection of IMLN metastases, but fluorodeoxyglucose avidity can be seen in both benign conditions and metastatic disease. US is helpful for staging, and US-guided fine-needle aspiration can be performed in cases of suspected IMLN metastasis. Management of suspicious IMLNs identified on imaging is typically with chemotherapy and radiation, as surgical excision does not provide survival benefit and is performed only in rare cases.

Effect of Breast Irradiation on Cardiac Disease in Women Enrolled in BCIRG-001 at 10-Year Follow-Up.

PURPOSE: To investigate cardiac toxicity associated with breast radiation therapy (RT) at 10-year follow-up in BCIRG-001, a phase 3 trial comparing adjuvant anthracycline chemotherapy (fluorouracil, doxorubicin, and cyclophosphamide) with anthracycline-taxane chemotherapy (docetaxel, doxorubicin, and cyclophosphamide) in women with lymph node-positive early breast cancer. METHODS AND MATERIALS: Prospective data from all 746 patients in the control arm (fluorouracil, doxorubicin, and cyclophosphamide) of BCIRG-001 at 10-year follow-up were obtained from Project Data Sphere. Cardiac toxicities examined included myocardial infarction (MI), heart failure (HF), arrhythmias, and relative and absolute left ventricular ejection fraction decrease of >20% from baseline. Toxicities were compared between patients who received RT versus no RT, left-sided RT versus no RT, and internal mammary nodal RT versus no RT. RESULTS: Of the 746 patients, 559 (75%) received RT to a median dose of 50 Gy. Myocardial infarction occurred in 3 RT patients (0.5%) versus 6 no-RT patients (3%) (P=.01). Heart failure was seen in 15 RT patients (2.7%) versus 3 no-RT patients (1.6%) (P=.6). Among these, 35 RT patients (18%) had a left ventricular ejection fraction relative decrease of >20% baseline versus 7 (10%) who did not receive RT (P=.1). Arrhythmias were more common in RT patients (3.2%) versus no-RT patients (0%) (P=.01). On univariable and multivariable analysis HF was not significantly associated with RT, and MI was negatively associated with RT. CONCLUSIONS: In this retrospective analysis of prospective toxicity outcomes, there is an increased risk of arrhythmias but no clear evidence of significantly increased risk of MI or HF at 10 years in lymph node-positive women treated with breast RT and uniform adjuvant doxorubicin-based chemotherapy. Given the low incidence of these outcomes, studies with larger numbers are needed to confirm our findings.

The effect of post-mastectomy radiation in women with one to three positive nodes enrolled on the control arm of BCIRG-005 at ten year follow-up.

BACKGROUND AND PURPOSE: We evaluated the effect of post-mastectomy radiation (PMRT) in 1-3 positive lymph nodes (LN) in patients who received uniform modern systemic therapy. MATERIALS AND METHODS: Cohort study using individual data collected for 1,649 node-positive women who received doxorubicin/cyclophosphamide with sequential docetaxel in 2000-2003 on the control arm of BCIRG-005. All women underwent mastectomy or lumpectomy and axillary LN dissection. PMRT was given at investigator's discretion. RESULTS: A total of 523 women with 1-3 positive LN underwent mastectomy and 39% (206/523) received PMRT. With a median follow-up of 10years, PMRT improved loco-regional control (LRC) from 91% to 98% (p=0.001) but had no effect on overall survival (OS) (84% vs. 86%, p=0.9). On multivariate analysis, PMRT improved local control (LC) (hazard ratio, 0.14; 95% CI, 0.03-0.62; p=0.01) and LRC (hazard ratio, 0.15; 95% CI, 0.04-0.50; p=0.002). PMRT did not significantly impact OS on multivariate analysis (hazard ratio, 0.91; 95% CI, 0.55-1.51; p=0.7). Results remained consistent with the use of propensity score analysis. CONCLUSIONS: In this cohort of patients with N1 disease treated with modern systemic therapy, PMRT improves LRC but has no effect on OS. The rates of OS were excellent, irrespective of adjuvant radiation.

Comparative patient-centered outcomes (health state and adverse sexual symptoms) between adjuvant brachytherapy versus no adjuvant brachytherapy in early stage endometrial cancer.

PURPOSE: To determine a relationship between sexual functioning and health state among survivors of stage I endometrial cancer, and to examine whether adjuvant intravaginal radiotherapy (IVRT) affects these measures compared to hysterectomy alone. METHODS: Two hundred five survivors (>1 year from surgery) completed questionnaires containing the EuroQol (EQ5D) and the Female Sexual Function Index (FSFI). A total of 136 (66.3 %) underwent surgery alone, and 69 (33.7 %) received IVRT. Pearson correlation was used to correlate FSFI and EQ5D-Health State scores. Multivariable regression was performed to measure the impact of IVRT on sexual functioning and health state. RESULTS: A majority of patients (80 %) met criteria for sexual dysfunction by FSFI < 26.5. A significant correlation was detected between FSFI and EQ5D scores (Pearson correlation = 0.21, p = 0.003). Compared to the IVRT group, the surgery group was younger (p = 0.001) and trended toward more frequent use of minimally invasive surgery versus laparotomy (p = 0.08). Otherwise, the two groups were well balanced with respect to demographics, comorbidities, and baseline sexual activity. Controlling for age and surgery type, IVRT was not associated with poorer health state or sexual function. Receipt of laparotomy was associated with both poorer health state and sexual function (p = 0.0156 and p = 0.0247, respectively). CONCLUSIONS: Sexual functioning was generally poor among endometrial cancer survivors; however, those with improved FSFI scores tended to have superior health states. IVRT was not a significant risk factor; however, receipt of laparotomy appeared to be associated with poorer sexual functioning and health state.

Adult rhabdomyosarcoma survival improved with treatment on multimodality protocols.

PURPOSE: Rhabdomyosarcoma (RMS) is a pediatric sarcoma rarely occurring in adults. For unknown reasons, adults with RMS have worse outcomes than do children. METHODS AND MATERIALS: We analyzed data from all patients who presented to Memorial Sloan-Kettering Cancer Center between 1990 and 2011 with RMS diagnosed at age 16 or older. One hundred forty-eight patients met the study criteria. Ten were excluded for lack of adequate data. RESULTS: The median age was 28 years. The histologic diagnoses were as follows: embryonal 54%, alveolar 33%, pleomorphic 12%, and not otherwise specified 2%. The tumor site was unfavorable in 67% of patients. Thirty-three patients (24%) were at low risk, 61 (44%) at intermediate risk, and 44 (32%) at high risk. Forty-six percent were treated on or according to a prospective RMS protocol. The 5-year rate of overall survival (OS) was 45% for patients with nonmetastatic disease. The failure rates at 5 years for patients with nonmetastatic disease were 34% for local failure and 42% for distant failure. Among patients with nonmetastatic disease (n=94), significant factors associated with OS were histologic diagnosis, site, risk group, age, and protocol treatment. On multivariate analysis, risk group and protocol treatment were significant after adjustment for age. The 5-year OS was 54% for protocol patients versus 36% for nonprotocol patients. CONCLUSIONS: Survival in adult patients with nonmetastatic disease was significantly improved for those treated on RMS protocols, most of which are now open to adults.

Factors influencing urinary symptoms 10 years after permanent prostate seed implantation.

PURPOSE: We investigated the factors that influenced urinary symptoms in the first 10 years after prostate brachytherapy. MATERIALS AND METHODS: A total of 1,932 men were treated with prostate brachytherapy alone or with external beam irradiation and followed a mean of 6.8 years. The influence of pretreatment American Urological Association symptom score (7 or less, 8 to 19, 20 or greater), external beam radiotherapy, (125)I or (103)Pd, biological effective dose, age, prostate size and hormone therapy on the change in American Urological Association symptom score (11,491) was compared. RESULTS: The mean change from initial score (7.4) was 11.4, 5.5, 3.3, 2.7, 1.5, 1.2, 1, 1, 1, 1, 1.3 and 1.4 points at 3, 6 months and 1 to 10 years, respectively (p <0.001). Factors that resulted in a greater increase in urinary symptoms at year 1 were low pretreatment score (p <0.001), no hormonal therapy (p <0.001), younger age (p = 0.046) and higher biological effective dose (p = 0.025). At 10 years patients with an initial score of 20 or greater had an average decrease of 11 points compared to a decrease of 0.9 for an initial score of 8 to 19 and an increase of 2.7 for an initial score of 7 or less (p <0.001). On linear regression the scores at 1 year were influenced by initial score (p <0.001), biological effective dose (p = 0.022), prostate size (p <0.001) and hormonal therapy (p = 0.009). At 10 years only the pretreatment score remained significant (p <0.001). CONCLUSIONS: There is minimal change in mean American Urological Association symptom score (1.4 points) 10 years after prostate brachytherapy. Patients presenting with high initial scores have the greatest improvement from baseline. Biological effective dose, external beam radiotherapy, hormonal therapy, isotope, patient age and prostate size do not appear to influence long-term urinary symptoms.