A Survey of Practice Patterns for Clinical Nodal Staging Prior to Neoadjuvant Chemotherapy in Breast Cancer.

BACKGROUND: The importance of clinical staging in breast cancer has increased owing to the wide use of neoadjuvant systemic therapy (NST). This study aimed to investigate the current practice patterns regarding clinical nodal staging in breast cancer in real-world settings. MATERIALS AND METHODS: A web-based survey was administered to board-certified oncologists in Korea, including breast surgical, medical, and radiation oncologists, from January to April 2022. The survey included 19 general questions and 4 case-based questions. RESULTS: In total, 122 oncologists (45 radiation, 44 surgical, and 33 medical oncologists) completed the survey. Among them, 108 (88%) responded that clinical staging before NST was primarily performed by breast surgeons. All the respondents referred to imaging studies during nodal staging. Overall, 64 (52.5%) responders determined the stage strictly based on the radiology reports, whereas 58 (47.5%) made their own decision while noting radiology reports. Of those who made their own decisions, 88% referred to the number or size of the suspicious node. Of the 75 respondents involved in prescribing regimens for neoadjuvant chemotherapy, 58 (77.3%) responded that the reimbursement regulations in the selection of NST regimens affected nodal staging in clinical practice. In the case-based questions, high variability was observed among the clinicians in the same cases. CONCLUSIONS: Diverse assessments by specialists owing to the lack of a clear, harmonized staging system for the clinical nodal staging of breast cancer can lead to diverse practice patterns. Thus, practical, harmonized, and objective methods for clinical nodal staging and for the outcomes of post-NST response are warranted for appropriate treatment decisions and accurate outcome evaluation.

Comparison of initial and sequential salvage brain-directed treatment in patients with 1-4 vs. 5-10 brain metastases from breast cancer (KROG 16-12).

PURPOSE: We aimed to compare the initial and salvage brain-directed treatment and overall survival (OS) between patients with 1-4 brain metastases (BMs) and those with 5-10 from breast cancer (BC). We also organized a decision tree to select the initial whole-brain radiotherapy (WBRT) for these patients. METHODS: Between 2008 and 2014, 471 patients were diagnosed with 1-10 BMs. They were divided into two groups based on the number of BM: 1-4 BMs (n = 337) and 5-10 BMs (n = 134). Median follow-up duration was 14.0 months. RESULTS: Stereotactic radiosurgery (SRS)/fractionated stereotactic radiotherapy (FSRT) was the most common treatment modality (n = 120, 36%) in the 1-4 BMs group. In contrast, 80% (n = 107) of patients with 5-10 BMs were treated with WBRT. The median OS of the entire cohort, 1-4 BMs, and 5-10 BMs was 18.0, 20.9, and 13.9 months, respectively. In the multivariate analysis, the number of BM and WBRT were not associated with OS, whereas triple-negative BC and extracranial metastasis decreased OS. Physicians determined the initial WBRT based on four variables in the following order: number and location of BM, primary tumor control, and performance status. Salvage brain-directed treatment (n = 184), mainly SRS/FSRT (n = 109, 59%), prolonged OS by a median of 14.3 months. CONCLUSION: The initial brain-directed treatment differed notably according to the number of BM, which was chosen based on four clinical factors. In patients with ≤ 10 BMs, the number of BM and WBRT did not affect OS. The major salvage brain-directed treatment modality was SRS/FSRT and increased OS.

Near-maximum rib dose is the most relevant risk factor for ipsilateral spontaneous rib fracture: a dosimetric analysis of breast cancer patients after radiotherapy.

PURPOSE: Spontaneous rib fracture (SRF) is a common late complication in treated breast cancer patients. This study evaluated the incidence and risk factors of ipsilateral SRF after radiotherapy (RT) in breast cancer patients. In addition, we identified dosimetric parameters that were significantly associated with ipsilateral SRF. METHODS: We retrospectively reviewed 2204 patients with breast cancer who underwent RT between 2014 and 2016, and were followed up with bone scans. We evaluated clinical risk factors for ipsilateral SRF. Dose-volume histogram analysis was also performed for patients (n = 538) whose dosimetric data were available. All ipsilateral ribs were manually delineated, and dosimetric parameters of the ribs were converted into the equivalent dose in 2 Gy fractions (EQD2). RESULTS: Most of the patients with SRF (87.3%) were asymptomatic, and the remaining symptomatic patients complained of mild tenderness or chest wall discomfort; these symptoms all resolved within 6 months without any treatment. Ipsilateral SRF occurred in 14.5% of patients 3 years after RT. The median time to develop ipsilateral SRF was 15 months. In dosimetric analysis, near-maximum rib dose (D2cc) best predicted ipsilateral SRF. The cut-off value of D2cc was EQD2 52 Gy, as determined by receiver operating characteristic analysis. In multivariate analysis including dosimetric variables, D2cc EQD2 ≥ 52 Gy was the only significant risk factor for ipsilateral SRF. CONCLUSION: Our data demonstrated that near-maximum rib dose was the best dosimetric parameter to predict ipsilateral SRF in RT-treated breast cancer patients. In addition, our results suggest that patients who received RT with exceeding rib dose cut-off value and had ipsilateral SRF on bone scan be recommended routine follow-up without additional imaging tests.

Validation of a nomogram for predicting the risk of lymphedema following contemporary treatment for breast cancer: a large multi-institutional study (KROG 20-05).

PURPOSE: We previously constructed a nomogram for predicting the risk of arm lymphedema following contemporary breast cancer treatment. This nomogram should be validated in patients with different background characteristics before use. Therefore, we aimed to externally validate the nomogram in a large multi-institutional cohort. METHODS: Overall, 8835 patients who underwent breast cancer surgery during 2007-2017 were identified. Data of variables in the nomogram and arm lymphedema were collected. The nomogram was validated externally using C-index and integrated area under the curve (iAUC) with 1000 bootstrap samples and by calibration plots. RESULTS: Overall, 1377 patients (15.6%) developed lymphedema. The median time from surgery to lymphedema development was 11.4 months. Lymphedema rates at 2, 3, and 5 years were 11.2%, 13.1%, and 15.6%, respectively. Patients with lymphedema had significantly higher body mass index (median, 24.1 kg/m2 vs. 23.4 kg/m2) and a greater number of removed nodes (median, 17 vs. 6) and more frequently underwent taxane-based chemotherapy (85.7% vs. 41.9%), total mastectomy (73.1% vs. 52.1%), conventionally fractionated radiotherapy (71.9% vs. 54.2%), and regional nodal irradiation (70.7% vs 22.4%) than those who did not develop lymphedema (all P < 0.001). The C-index of the nomogram was 0.7887, and iAUC was 0.7628, indicating good predictive accuracy. Calibration plots confirmed that the predicted lymphedema risks were well correlated with the actual lymphedema rates. CONCLUSION: This nomogram, which was developed using factors related to multimodal breast cancer treatment and was validated in a large multi-institutional cohort, can well predict the risk of breast cancer-related lymphedema.

Prognostic impact of neutrophilia and lymphopenia on survival in anal cancer treated with definitive concurrent chemoradiotherapy: a retrospective multicenter study.

PURPOSE: This study evaluated the prognostic value of leukocyte, lymphocyte, and neutrophil counts in anal cancer patients undergoing concurrent chemoradiotherapy (CCRT). METHODS: Multi-institutional retrospective data review included 148 non-metastatic anal cancer patients treated with definitive CCRT with 5-fluorouracil plus mitomycin C between the year 2001 and 2019. The median radiation dose to the primary tumor was 54 Gy with a median pelvic dose of 45 Gy. Median follow-up duration was 56 months, and complete blood cell counts were analyzed from baseline to 1 year after the completion of radiotherapy. RESULTS: Although most patients showed a normal number of blood cells before treatment, 6.1% and 4.1% of patients showed leukocytosis (> 10,000/µl) and neutrophilia (> 7500/µl), respectively. After the initiation of treatment, seven patients (4.7%) displayed grade 4 lymphopenia (< 200/µl) at 1 month. Patients with initial leukocytosis showed inferior progression- and locoregional progression-free survival, and neutrophilia was a prognostic factor in all survival outcomes. Grade 4 lymphopenia at 1 month was also significantly associated with overall, progression-, and distant metastasis-free survival. On multivariate analyses, baseline neutrophilia was associated with 56.8-, 22.6-, 10.7-, and 23.0-fold increased risks of death, disease relapse, locoregional progression, and distant metastasis, respectively. Furthermore, lymphocytes < 200/µl at 1 month was linked to 6.8-, 5.4-, and 6.3-fold increased risks for death, disease relapse, and distant metastasis, respectively. CONCLUSION: The number of leukocytes, lymphocytes, and neutrophils readily acquired from routine blood tests before and during treatment could be an independent prognostic factor of survival in patients with anal cancer.

Consumer-grade sleep trackers are still not up to par compared to polysomnography.

PURPOSE: Although polysomnography (PSG) is the gold standard for monitoring sleep, it has many limitations. We aimed to prospectively determine the validity of wearable sleep-tracking devices and smartphone applications by comparing the data to that of PSGs. METHODS: Patients who underwent one night of attended PSG at a single institution from January, 2015 to July 2019 were recruited. Either a sleep application or wearable device was used simultaneously while undergoing PSG. Nine smartphone applications and three wearable devices were assessed. RESULTS: We analyzed the results of 495 cases of smartphone applications and 170 cases of wearables by comparing each against PSG. None of the tested applications were able to show a statistically significant correlation between sleep efficiency, durations of wake time, light sleep or deep sleep with PSG. Snore time correlated well in both of the two applications which provided such information. Deep sleep duration and WASO measured by two of the three wearable devices correlated significantly with PSG. Even after controlling for transition count and moving count, the correlation indices of the wearables did not increase, suggesting that the algorithms used by the wearables were not largely affected by tossing and turning. CONCLUSIONS: Most of the applications tested in this study showed poor validity, while wearable devices mildly correlated with PSG. An effective use for these devices may be as a tool to identify the change seen in an individual's sleep patterns on a day-to-day basis, instead of as a method of detecting absolute measurements.

New brain metastases after whole-brain radiotherapy of initial brain metastases in breast cancer patients: the significance of molecular subtypes (KROG 16-12).

PURPOSE: To identify the risk factors leading to new brain metastases (BM) following brain-directed treatment for initial BM resulting from breast cancer (BC). METHODS: In this multi-institutional study, 538 BC patients with available follow-up imaging after brain-directed treatment for initial BM were analyzed. Tumor molecular subtypes were classified as follows: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-, n = 136), HER2-positive (HER2+, n = 253), or triple-negative BC (TNBC, n = 149). RESULTS: In 37.4% of patients, new BM emerged at a median of 10.5 months after brain-directed treatment for initial BM. The 1-year actuarial rate of new BM for HR+/HER2-, HER2+, and TNBC were 51.9%, 44.0%, and 69.6%, respectively (p = 0.008). Initial whole-brain radiotherapy (WBRT) reduced new BM rates (22.5% reduction at 1 year, p < 0.001) according to molecular subtype (HR+/HER2-, 42% reduction at 1 year, p < 0.001; HER2+, 18.5%, p = 0.004; TNBC, 16.9%, p = 0.071). Multivariate analysis revealed an increased risk of new BM for the following factors: shorter intervals between primary BC diagnoses and BM (p = 0.031); TNBC (relative to HR+/HER2-) (p = 0.016); presence of extracranial metastases (p = 0.019); number of BM (>4) (p < 0.001); and BM in both tentorial regions (p = 0.045). Anti-HER2 therapy in HER2+ patients (p = 0.013) and initial use of WBRT (p < 0.001) significantly lowered new BM development. CONCLUSIONS: Tumor molecular subtypes were associated with both rates of new BM development and the effectiveness of initial WBRT. Anti-HER2 therapy in HER2+ patients significantly lowered new BM occurrence.

Risk Stratification Using Neoadjuvant Rectal Score in the Era of Neoadjuvant Chemoradiotherapy: Validation With Long-term Outcome Data.

BACKGROUND: Despite the widespread use of neoadjuvant chemoradiotherapy, there is no prognostic surrogate marker established in locally advanced rectal cancer. OBJECTIVE: This study evaluated the role of neoadjuvant rectal score as a prognostic factor to stratify individual-level risks of survival and tumor recurrence. DESIGN: This is a retrospective study. SETTINGS: This study was conducted at the Seoul National University Hospital. PATIENTS: A total of 397 patients who underwent chemoradiotherapy plus total mesorectal excision were analyzed. INTERVENTIONS: There was no intervention. MAIN OUTCOME MEASURES: Harrell C statistic and receiver operating characteristic analysis, as well as Cox regression analysis, were used to assess the prognostic strength. RESULTS: The low (<8), intermediate (8-16), and high (>16) neoadjuvant rectal score groups included 91 (23%), 208 (52%), and 98 patients (25%). A high neoadjuvant rectal score was independently associated with inferior overall survival and disease-free survival (p = 0.011 and 0.008). Regarding the prognostic models adjusted for neoadjuvant rectal score (I) and ypT/N stage (II), the c-index was higher in model I (0.799 and 0.787, p = 0.009 for overall survival; 0.752 and 0.743, p = 0.093 for disease-free survival). The predictive ability of the neoadjuvant rectal score was superior to tumor regression grade, ypT, and ypN in the receiver operating characteristic analyses (p < 0.05 for all). Adjuvant chemotherapy was associated with better overall and disease-free survival (p = 0.003 and 0.052) in the high neoadjuvant rectal score group. LIMITATIONS: Potential selection bias attributed to the retrospective study design was a limitation. CONCLUSIONS: We verified the applicability of the neoadjuvant rectal score to stratify the relapse risk at the individual level for patients with stage II/III rectal cancer undergoing neoadjuvant chemoradiotherapy. Additional studies are needed to validate the usability of neoadjuvant rectal score levels as a determinant of adjuvant strategy. See Video Abstract at http://links.lww.com/DCR/B354. ESTRATIFICACIÓN DE RIESGO UTILIZANDO LA PUNTUACIÓN RECTAL NEOADYUVANTE EN LA ERA DE LA QUIMIORRADIOTERAPIA NEOADYUVANTE: VALIDACIÓN CON DATOS DE RESULTADOS A LARGO PLAZO: A pesar del uso generalizado de la quimiorradioterapia neoadyuvante, no existe un marcador subrogado pronóstico establecido en el cáncer de recto localmente avanzado.Este estudio evaluó el papel de la puntuación rectal neoadyuvante como factor pronóstico para estratificar los riesgos a nivel individual de supervivencia y recurrencia tumoral.Este es un estudio retrospectivo.Este estudio se realizó en el Hospital de la Universidad Nacional de Seúl.Se analizaron un total de 397 pacientes que se sometieron a quimiorradioterapia más escisión mesorrectal total.No hubo intervención.El análisis estadístico C de Harrell y las características operativas del receptor, así como el análisis de regresión de Cox, se utilizaron para evaluar la fuerza pronóstica.Los grupos de puntaje rectal neoadyuvante bajo (<8), intermedio (8-16) y alto (> 16) incluyeron 91 (23%), 208 (52%) y 98 (25%) pacientes, respectivamente. Una puntuación rectal neoadyuvante alta se asoció independientemente con una supervivencia general y una supervivencia libre de enfermedad inferiores (p = 0.011 y 0.008, respectivamente). Con respecto a los modelos pronósticos ajustados por la puntuación rectal neoadyuvante (I) y el estadio ypT/N (II), el índice c fue mayor en el modelo I (0.799 y 0.787, p = 0.009 para la supervivencia general; 0.752 y 0.743, p = 0.093 para supervivencia libre de enfermedad). La capacidad predictiva de la puntuación rectal neoadyuvante fue superior al grado de regresión tumoral, ypT y ypN en los análisis de características operativas del receptor (p <0.05 para todos). La quimioterapia adyuvante se asoció con una mejor supervivencia global y libre de enfermedad (p = 0.003 y 0.052, respectivamente) en el grupo de puntaje rectal neoadyuvante alto.El sesgo de selección potencial debido al diseño retrospectivo del estudio fue la limitación.Verificamos la aplicabilidad de la puntuación rectal neoadyuvante para estratificar el riesgo de recurrencia a nivel individual para pacientes con cáncer rectal en estadio II/III sometidos a quimiorradioterapia neoadyuvante. Se necesitan más estudios para validar la usabilidad de los niveles de puntuación rectal neoadyuvante como determinante de la estrategia adyuvante. Consulte Video Resumen en http://links.lww.com/DCR/B354.

Effect of Intermittent Hypoxia on Metabolic Syndrome and Insulin Resistance in the General Male Population.

Background and objectives: Obstructive sleep apnea (OSA) is closely associated with insulin resistance (IR) and is an independent risk factor for incident type 2 diabetes mellitus (T2DM). Most studies evaluate the correlation between OSA and IR in only obese or T2DM patients. Therefore, we tried to investigate the effect of OSA on metabolic syndrome and IR in the general healthy male population. Materials and Methods: 184 subjects who visited a preventive health examination program were recruited for this study. All subjects received overnight polysomnography by a portable device (Watch-PAT 200). We examined several metabolic parameters and a homeostasis model of assessment for insulin resistance index (HOMA-IR). The subjects were divided into three groups by AHI (Apnea-hyponea index): normal group (AHI < 5), mild OSA group (5 ≤ AHI < 15), and moderate-severe OSA group (AHI ≥ 15). They were also divided into two groups according to minimum oxygen saturation: low group, Min-SpO2 < 88%; and high group, Min-SpO2 ≥ 88%. Results: Parameters of metabolic syndrome, including waist circumference, systolic and diastolic blood pressure, triglyceride, and high-density lipoprotein cholesterol showed significant differences among the AHI groups. Furthermore, HOMA-IR showed significant differences among the AHI groups. Those parameters, including metabolic syndrome and HOMA-IR, also showed differences between Min-SpO2 groups. Conclusions: In summary, this study helps confirm that AHI is associated with HOMA-IR in the general male population. Furthermore, the severity of AHI correlated with the parameters of metabolic syndrome. Therefore, AHI might be an indicator for evaluating both T2DM and metabolic syndrome, even in the general male population.

Hypofractionated whole breast irradiation after conservative surgery for patients aged less than 60 years: a multi-centre comparative study.

Background: For decades, conventional fractionated whole breast irradiation (CF-WBI) was used after breast conserving surgery (BCS). Pivotal phase-3 trials on hypofractionated-WBI (HF-WBI) showed its non-inferiority as compared to CF-WBI. However, younger patients are often not treated with HF-WBI. The aim of this multi-centre comparative study is to confirm the safety of HF-WBI in a real-life series of younger patients.Material and methods: Between 2010 and 2016, a total of 786 patients aged less than 60 years old with early-stage breast cancer were treated with postoperative WBI after BCS in three breast cancer centres: 340 underwent HF-WBI while 446 were treated with CF-WBI. Acute toxicity was evaluated at the end of WBI. Late toxicity was evaluated at 6, 12, 24 and 36 months.Results: At univariate logistic analysis, hypofractionation showed a significant protective effect in terms of acute oedema, acute wet desquamation, chronic oedema, chronic erythema/pigmentation and breast fibrosis. At multivariate logistic analysis, hypofractionation was an independent significant factor for acute oedema, acute wet desquamation, and chronic oedema. There were not differences in tumour-related outcomes.Conclusions: HF-WBI showed significantly improved outcomes in terms of acute skin oedema, wet desquamation and chronic skin oedema. HF-WBI after BCS should be strongly encouraged to replace CF-WBI independently of age.

Physical activity status in relation to quality of life and dietary habits in breast cancer survivors: subset analyses of KROG 14-09 nationwide questionnaire study.

PURPOSE: We investigated the relationship of physical activity with dietary habits and quality of life (QoL) in breast cancer survivors in accordance with the recommendations of the American Cancer Society. METHODS: Data of 928 breast cancer survivors were obtained from the KROG 14-09 study to measure QoL in early phase after adjuvant radiotherapy. According to the extent of physical activity, survivors were divided into four groups: inactivity (0-149 min/week, N = 144), regular activity (150-450 min/week, N = 309), moderate activity (451-900 min/week, N = 229), and marked activity (901-1800 min/week, N = 164) excluding hyperactivity (> 1800 min/week, N = 82) as it is a difficult condition to recommend to survivors. Global physical activity questionnaire, 5-dimensional questionnaire by EuroQoL (EQ-5D-3L), QoL Questionnaire-breast cancer (QLQ-BR23) from EORTC, and dietary habits were surveyed. A linear-to-linear association test for EQ-5D-3L and Kruskal-Wallis analysis for QLQ-BR23 and dietary habit were conducted. RESULTS: Overall, 15.5% respondents (144/928) were classified as physically inactive. The trends of frequent intake of fruits (p = 0.001) and vegetable (p = 0.005) and reluctance toward fatty food (p < 0.001) were observed in physically active groups. Mobility (p = 0.021) and anxiety (p = 0.030) of EQ-5D-3L, and systemic therapy side effect (p = 0.027) and future perspective (p = 0.008) of QLQ-BR23 were better in physically active groups besides body image (p = 0.003) for the survivors with breast-conserving surgery. However, moderate and marked activities did not further improve QoL than regular activity. CONCLUSION: Physicians and care-givers have to pay attention to inactive survivors to boost their physical activity, thereby facilitating a better QoL and dietary habit.

Questionnaire study of the dietary habits of breast cancer survivors and their relationship to quality of life (KROG 14-09).

We evaluated the dietary habits of breast cancer survivors and investigated the relationship with quality of life (QoL), with 1,156 survivors recruited from 17 institutions. We used the Questionnaire Survey of Dietary Habits of Korean Adults (Q-DH-KOR) comprising 25 questions. The following indices were derived as follows: (1) quality of healthy dietary habits (Q-HD)-eight questions on number of meals, regularity, quantity, duration, skipping breakfast, dinner with companion(s), overeating and late-night snacks; (2) habits of nutritional balance (H-NB)-questions on consuming five food categories (grains, fruits, proteins, vegetables and dairy products); and (3) habits of unhealthy foods (H-UF)-questions on consuming three food categories (fatty, instant and fast foods). The times and regularity of meals, frequency of skipping breakfast, dinner with companion(s) and overeating were better in groups with high symptomatic and functional QoL. Symptomatic QoL positively affected Q-HD and H-NB (p < 0.001 and p = 0.024 respectively) and negatively affected H-UF (p = 0.02). Breast cancer survivors more frequently ate from the fruit, protein and vegetable categories than did the control group, with lower H-UF and higher Q-HD values (p < 0.001 and p < 0.001 respectively). Our findings supported the relationship between QoL and dietary habit and showed healthier dietary habits of breast cancer survivors than controls.

Effects of trastuzumab on locoregional recurrence in human epidermal growth factor receptor 2-overexpressing breast cancer patients treated with chemotherapy and radiotherapy.

PURPOSE: In the present study, the ability of adjuvant trastuzumab to reduce locoregional recurrence in patients with human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer receiving adjuvant chemotherapy and radiotherapy (RT) was investigated. MATERIALS AND METHODS: We retrospectively included 520 patients with HER2-overexpressing breast cancer who received surgery followed by adjuvant RT and cytotoxic chemotherapy from 2003 to 2011. Adjuvant trastuzumab was administered to 286 patients. Propensity score matching was conducted to compare trastuzumab-treated and non-treated cohorts. RESULTS: Median follow-up duration was 7.1 years (range 1.1-14.1 years). Propensity score matching yielded 171 matched pairs of patients with no significantly different clinical factors. An improved 7-year locoregional control (LRC) rate was observed in the trastuzumab-treated cohort compared with the non-treated cohort (95.6% vs. 89.9%, p = 0.014). Based on multivariate analysis, hormone receptor negativity (hazard ratio [HR] = 5.348, p = 0.007), positive lymph node ratio > 0.25 (HR = 2.549, p = 0.040), and lack of adjuvant trastuzumab (HR = 3.401, p = 0.017) were identified as significant risk factors for poor LRC. Adjuvant trastuzumab significantly reduced the locoregional recurrence rate in patients with one or two risk factors (7-year LRC = 95.0% vs. 84.2%, p = 0.007); however, the benefit of adjuvant trastuzumab was non-significant in patients with no risk factors (7-year LRC = 95.8% vs. 97.9%, p = 0.75). CONCLUSIONS: Adjuvant trastuzumab improved LRC in patients with HER2-overexpressing breast cancer receiving adjuvant RT and cytotoxic chemotherapy, especially in hormone receptor-negative, HER2-enriched subtype, and high positive lymph node ratio breast cancer.

Malignant and borderline phyllodes tumors of the breast: a multicenter study of 362 patients (KROG 16-08).

PURPOSE: To identify risk factors for local recurrence (LR) and investigate roles of adjuvant local therapy for malignant and borderline phyllodes tumors of the breast. METHODS: From 1981 to 2014, 362 patients with malignant (n = 235) and borderline (n = 127) phyllodes tumors were treated by breast-conserving surgery (BCS) or total mastectomy (TM) at 10 centers. Thirty-one patients received adjuvant radiation therapy (RT), and those who received adjuvant chemotherapy were excluded from the study. RESULTS: Median follow-up was 5 years. LR developed in 60 (16.6%) patients. Regional recurrence occurred in 2 (0.6%) patients and distant metastasis (DM) developed in 19 (5.2%) patients. Patients receiving BCS (p = 0.025) and those not undergoing adjuvant RT (p = 0.041) showed higher LR rates. For malignant subtypes, local control (LC) rates at 5 years for BCS alone, BCS with adjuvant RT, TM alone, and TM with adjuvant RT were 80.7, 93.3, 92.4, and 100%, respectively (p = 0.033). Multivariate analyses revealed BCS alone, tumor size ≥ 5 cm, and positive margins as independent risk factors for LR. Margin-positive BCS alone showed poorest LC regardless of tumor size (62.5%, p = 0.007). For margin-negative BCS alone, 5-year LC rates for tumors ≥ 5 cm versus those < 5 cm were 71.8% versus 89.5% (p = 0.012). For borderline subtypes, only positive margins (p = 0.044) independently increased the risk of LR. DM developed exclusively in malignant subtypes and a prior LR event increased the risk of DM by sixfold (HR 6.2, 95% CI 1.6-16.1, p = 0.001). CONCLUSIONS: Malignant and borderline phyllodes tumors with positive margins after surgery have high LR rates. After treatment by margin-negative BCS alone, patients with large malignant phyllodes tumors ≥ 5 cm also have heightened risk of LR. Thus, such patients should be considered for additional local therapy.

Chest wall recurrence in pT1-2N0-1 breast cancer patients after mastectomy without radiotherapy.

PURPOSE: In correlation with the nodal status in the era of modern radiotherapy, the chest wall recurrence (CWR) rate was investigated in pT1-2N0-1 breast cancer patients after a mastectomy without post-mastectomy radiotherapy (PMRT). METHODS: The data from the patients participating in two South Korean multi-institutional studies (KROG 14-22; N = 1842 and KROG 14-23; N = 1382) were analyzed. In total, 3224 pT1-2N0-1 breast cancer patients who underwent mastectomy without PMRT were analyzed. RESULTS: The median follow-up time was 72.2 months (range 0.8-125.2 months). The overall CWRs during the follow-up period were 1.68% in N0 patients and 2.82% in N1 patients. There was no statistically significant difference in 5-year and 10-year CWR-free survival (CWRFS) between the N0 and N1 patients. Of the 70 patients with CWR, 33 (1% of all the patients) had isolated CWR, and the 10-year overall survival rate in this group was 96.9%. After the propensity score matching of the N0 and N1 groups, there was still no difference in CWRFS by nodal status. CONCLUSIONS: The incidence of CWR in pT1-2N0-1 breast cancer patients is very low, especially with isolated recurrence. Also, the obtained data showed that the nodal status had no impact on CWRFS.

Adjuvant Chemoradiotherapy is Associated with Improved Survival for Patients with Resected Gallbladder Carcinoma: A Systematic Review and Meta-analysis.

BACKGROUND: The impact of adjuvant radiotherapy (ART) on survival from gallbladder carcinoma (GBC) remains underexplored, with conflicting results reported. A systematic review and meta-analysis was performed to clarify the impact of ART in GBC. METHODS: A systematic literature search of several databases was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, from inception to August 2016. Studies that reported survival outcomes for patients with or without ART after curative surgery were included. RESULTS: All the inclusion criteria was met by 14 retrospective studies including 9364 analyzable patients, but most of the studies had a moderate risk of bias. Generally, the ART group had more patients with unfavorable characteristics than the group that had surgery alone. Nevertheless, the pooled results showed that ART significantly reduced the risk of death (hazard ratio [HR], 0.54; 95% confidence interval [CI] 0.44-0.67; p < 0.001) and recurrence (HR 0.61; 95% CI 0.38-0.98; p = 0.04) of GBC compared with surgery alone. Exploratory analyses demonstrated a survival benefit from ART for a subgroup of patients with lymph node-positive diseases (HR 0.61; p < 0.001) and R1 resections (HR 0.55; p < 0.001), but not for patients with lymph node-negative disease (HR 1.06; p = 0.78). No evidence of publication bias was found (p = 0.663). CONCLUSIONS: This study is the first meta-analysis to evaluate the role of ART and to provide supporting evidence that ART may offer survival benefits, especially for high-risk patients. However, further confirmation with a randomized prospective study is needed to clarify the subgroup of GBC patients who would benefit most from ART.

The impact of perioperative CA19-9 change on the survival and recurrence patterns after adjuvant chemoradiotherapy in resectable extrahepatic cholangiocarcinoma.

BACKGROUNDS: Perioperative CA19-9 value in pancreato-biliary cancers has been recognized as a prognostic factor. Herein, we investigated survival differences and recurrence patterns after adjuvant chemoradiotherapy by perioperative CA19-9 change in surgically resected extrahepatic cholangiocarcinoma. METHODS: Patients were divided into those with preoperative normal CA19-9 (Group 1, n = 52), those with high preoperative and normalized postoperative CA19-9 (Group 2, n = 80), and those with both high pre- and postoperative CA19-9 (Group 3, n = 21). RESULTS: Depending on the group defined above, the 5-year overall survival (OS) (59.6%, 38.7%, and 9.5%, P < 0.001) and disease-free survival (55.8%, 31.2%, and 9.5%, P < 0.001) between the three groups differed. On multivariable analysis in patients other than group 1, poor prognosticators for OS were high postoperative CA19-9 (HR 2.26, P = 0.008) and N1 disease (HR 2.33, P = 0.001). Group 3, compared with group 2, showed higher distant metastasis rate, shorter disease-free interval, and higher CA19-9 at the time of recurrence. CONCLUSIONS: Survival and recurrence patterns after adjuvant chemoradiotherapy are significantly affected by perioperative CA19-9 change. This may have important implications in patient selection for adjuvant chemoradiotherapy and clinical trial design.

Preoperative MDCT Assessment of Resectability in Borderline Resectable Pancreatic Cancer: Effect of Neoadjuvant Chemoradiation Therapy.

OBJECTIVE: The purpose of this study is to evaluate the diagnostic performance of MDCT in assessing tumor resectability in patients with borderline resectable pancreatic cancers after receiving neoadjuvant chemoradiation therapy (CRT) in comparison with those undergoing upfront surgery. SUBJECTS AND METHODS: Thirty-seven patients with borderline resectable pancreatic cancers were randomly allocated to the neoadjuvant CRT group (arm 1; n = 18) or up-front surgery group (arm 2; n = 19). Three radiologists rated the likelihood of local resectability on a 5-point scale at preoperative MDCT in two separate sessions (session 1: post-CRT of arm 1, baseline of arm 2; session 2: using new imaging criteria reflecting the changes during CRT of arm 1). The AUC of each reviewer, as well as sensitivity, specificity, and accuracy based on consensus interpretation, were compared between arms and sessions. RESULTS: For local resectability (n = 30), AUC values at session 1 were 0.664, 0.669, and 0.588 for reviewers 1, 2, and 3, respectively, and were not significantly different between arms 1 (n = 15; 0.759, 0.713, and 0.593) and 2 (n = 15; 0.852, 0.685, and 0.722) (p > 0.05). In arm 1, MDCT sensitivity, specificity, accuracy were 22%, 100%, and 53%, respectively, at session 1 versus 78%, 67%, and 73%, respectively, at session 2 (p > 0.05). CONCLUSION: In patients with borderline resectable pancreatic cancers, neoadjuvant CRT did not significantly decrease the performance of MDCT for the prediction of local resectability. However, by considering post-CRT changes, such as nonprogression in tumor-vascular contact, MDCT may provide better sensitivity for locally resectable disease.

The Updated AJCC/TNM Staging System for Papillary Thyroid Cancer (8th Edition): From the Perspective of Genomic Analysis.

BACKGROUND: Recently, the American Joint Committee on Cancer published the 8th edition of its Cancer Staging Manual with major changes regarding the staging of thyroid cancer, including the raising of the age cutoff from 45 to 55 years. Using the clinical and genetic data of 505 papillary thyroid cancer (PTC) cases, we aimed to compare overall survival (OS) and recurrence-free survival (RFS) with different age cutoff values, and also investigate the efficacy of the new staging system on a genomic level. METHODS: We downloaded gene expression data, somatic mutation profile, copy number alteration data and clinical data of 505 PTC patients from The Cancer Genome Atlas data portal. We used multiple statistical analysis and multiplatform genomic analysis to evaluate the efficacy of the 8th edition. RESULTS: When using 55 years as the cutoff value for analyzing RFS, the Kaplan-Meier plot showed a significant p value but not when using 45 years (p = 0.006 vs. p = 0.493), but both cutoff values were significant when analyzing OS (p = 1.1 × 10-9 with age 55 vs. p = 4.4 × 10-5 with age 45). When looking at stage-dependent survival, both the 7th and 8th edition had significant p values (p = 0.048 vs. p = 3.1 × 10-9 in RFS and p = 5.9 × 10-10 vs. p = 2.2 × 10-10 in OS). Multiplatform genomic analysis showed patients ≥55 years had 103 differently expressed genes when compared with other age groups. Signaling pathway analysis revealed that patients ≥55 years had altered pathways associated with aggressiveness of thyroid cancer. CONCLUSION: In conclusion, this is the first study to show clinical and genetic evidence supporting the altered age cutoff point of 55 years in the AJCC 8th edition for PTC patients.

Role of Adjuvant Chemoradiotherapy for Duodenal Cancer: An Updated Analysis of Long-Term Follow-Up from Single Institution.

BACKGROUND: There are only limited data on the failure patterns after surgical resection for duodenal cancer, and the role of adjuvant chemoradiotherapy (CRT) also remains controversial. In this study, the treatment outcomes of surgery alone were compared to those of surgery plus adjuvant CRT for duodenal cancer. METHODS: Between January 1991 and February 2013, a total of 47 patients with duodenal cancer had pancreaticoduodenectomy, and their age ranged from 31 to 80 (median 62). Twenty-five patients (53%) underwent surgery alone, while 22 (47%) underwent surgery plus adjuvant CRT. Postoperative radiotherapy with concomitant 5-fluorouracil was given to tumor bed and regional lymph nodes up to 40-55.4 Gy. Median duration of follow-up was 31 months (range 6-286) for all patients and 90 months (range 14-286) for survivors. RESULTS: CRT (+) group included more patients with advanced nodal stage and overall stage group (p = 0.003 and 0.002, respectively). The 5-year overall survival rates were not different between CRT (-) and CRT (+) groups (50.1 vs. 46.7%, p = 0.794). CRT (+) group achieved a superior 5-year loco-regional relapse-free survival rate compared with CRT (-) group, but the difference did not reach a statistical significance (80.1 vs. 68.4%, p = 0.267). On multivariate analysis, however, the addition of CRT was the only favorable prognosticator predicting loco-regional relapse-free survival (p = 0.046). Two patients experienced grade 3 neutropenia during CRT. CONCLUSIONS: Adjuvant CRT after pancreaticoduodenectomy was correlated with an improved loco-regional control in duodenal cancer. Considering the high loco-regional recurrence in surgery alone group, CRT may be considered as adjuvant treatment.