Survival Outcomes and Patterns of Care for Stage II or III Resected Gastric Cancer by Race and Ethnicity.

Importance: Many multimodality treatment regimens exist for gastric adenocarcinoma, including neoadjuvant vs adjuvant chemotherapy, radiation, or both. Neoadjuvant therapy is recommended in the United States for patients with locally advanced gastric cancer; however, it is unknown whether the outcomes of neoadjuvant therapy are associated with race and ethnicity. Objective: To evaluate the differences in outcomes by race and ethnicity of patients with noncardia gastric cancer undergoing surgical procedures with and without neoadjuvant therapy. Design, Setting, and Participants: This retrospective cohort study examined the National Cancer Database from the American College of Surgeons for patients with clinical stage II or III gastric adenocarcinoma, excluding gastric cardia tumors, undergoing surgical resection procedures from January 2006 to December 2019. Statistical analysis was performed from December 2021 to May 2023. Exposure: Patients were stratified by race and ethnicity, and their outcomes were analyzed for those who received and did not receive neoadjuvant therapy. Main Outcomes and Measures: The Cox proportional hazard model was used to compare overall survival (OS) between racial and ethnic groups (Asian, Black, Hispanic, and White) overall and according to receipt of neoadjuvant therapy. Among those who received neoadjuvant therapy, proportional differences in pathological responses were calculated in each group. Results: Among a total of 6938 patients in the cohort, 4266 (61.4%) were male; mean (SD) age was 65.9 (12.8) years; 1046 (15.8%) were Asian, 1606 (24.3%) were Black, 1175 (17.8%) were Hispanic, and 3540 (53.6%) were White. Compared with other races and ethnicities, the group of White patients had significantly more who were 65 years or older with more comorbidities. White patients underwent surgical resection procedures alone without neoadjuvant or adjuvant therapy more frequently than other races and ethnicities. Asian and Black patients had the highest proportion of being downstaged or achieving pathological complete response after neoadjuvant therapy. In multivariate models, perioperative chemotherapy was associated with improved OS (HR, 0.79 [95% CI, 0.69-0.90]), whereas number of positive lymph nodes and surgical margins were associated with the largest decreases in OS. Asian and Hispanic race and ethnicity were associated with significantly improved OS compared with Black and White races (eg, Asian patients: HR, 0.64 [95% CI, 0.58-0.72]; and Hispanic patients: HR, 0.77 [95% CI, 0.69-0.85]). Black race was associated with improved OS compared with White race when receiving neoadjuvant therapy (HR, 0.78 [95% CI, 0.67-0.90]). Conclusions and Relevance: In this large nationwide cohort study of survival outcomes among patients with resected clinical stage II or III gastric cancer, there were significant differences in response to treatment and OS between different racial and ethnic groups.

Stereotactic Body Radiation Therapy for the Treatment of Locally Recurrent and Oligoprogressive Non-Small Cell Lung Cancer: A Single Institution Experience.

Objectives: To investigate the efficacy and safety of lung stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC) including oligorecurrent and oligoprogressive disease. Methods: Single-institution retrospective analysis of 60 NSCLC patients with 62 discrete lesions treated with SBRT between 2008 and 2017. Patients were stratified into three groups, including early stage, locally recurrent, and oligoprogressive disease. Group 1 included early stage local disease with no prior local therapy. Group 2 included locally recurrent disease after local treatment of a primary lesion, and group 3 included regional or well-controlled distant metastatic disease receiving SBRT for a treatment naive lung lesion (oligoprogressive disease). Patient/tumor characteristics and adverse effects were recorded. Local failure free survival (LFFS), progression free survival (PFS), and overall survival (OS) were estimated using the Kaplan Meier method. Results: At median follow-up of 34 months, 67% of the study population remained alive. The estimated 3-year LFFS for group 1, group 2, and group 3 patients was 95% (95% CI: 86%-100%), 82%(62% - 100%), and 83% (58-100%), respectively. The estimated 3-year PFS was 59% (42-83%), 40% (21%-78%), and 33% (12%-95%), and the estimated 3-year OS was 58% (41-82%), 60% (37-96%), and 58% (31-100%)), respectively for each group. When adjusted for age and size of lesion, no significant difference in OS, LFFS, and PFS emerged between groups (p > 0.05). No patients experienced grade 3 to 5 toxicity. Eighteen patients (29%) experienced grade 1 to 2 toxicity. The most common toxicities reported were cough and fatigue. Conclusions: Our data demonstrates control rates in group 1 patients comparable to historical controls. Our study also reveals comparable clinical results for SBRT in the treatment of NSCLC by demonstrating similar rates of LFFS and OS in group 2 and group 3 patients with locally recurrent and treatment naïve lung lesion with well-controlled distant metastatic disease.

Ductal Carcinoma in Situ in Young Women: Increasing Rates of Mastectomy and Variability in Endocrine Therapy Use.

BACKGROUND: Young women with ductal carcinoma in situ (DCIS) represent a unique cohort given considerations for future risk reduction and treatment effects on fertility and quality of life. We evaluated national patterns of care in the treatment of young women and the impact of those treatments on overall survival (OS). METHODS: Women younger than 50 years of age diagnosed with pure DCIS from 2004 to 2016 in the National Cancer Database (NCDB) were identified. Clinical, demographic, and choice of local therapy are summarized and trended over time. OS was analyzed using Cox proportional hazard models. RESULTS: A total of 52,150 women were identified, and the most common surgical treatment was breast-conservation surgery (BCS; 59%). Bilateral mastectomy (BM) increased in frequency from 2004 to 2016 (11-27%; p < 0.001). In women < 40 years of age, BM (39%) surpassed BCS (35%) in 2010 with a continued upward trend. On multivariable analysis, no OS benefit of BM (hazard ratio [HR] 0.99, p = 0.90) or unilateral mastectomy (UM; HR 0.98, p = 0.80) was observed when compared with BCS + radiation therapy (RT). Inferior OS was seen with BCS, Black race, estrogen receptor (ER)-negative, and tumor ≥ 2.5 cm (p ≤ 0.006). In ER+ patients, there was a significant difference in endocrine therapy (ET) use between BM (11%), UM (33%), and BCS (28%) compared with BCS + RT (64%, p < 0.001). CONCLUSION: The use of BM for DCIS is increasing in younger patients and now exceeds breast-conservation approaches in women < 40 years of age with no evidence of improved OS. Among ER+ patients, the rates of ET are lower in the BM, UM, and BCS-alone groups compared with BCS + RT.

Outcomes of HER2-positive non-metastatic breast cancer patients treated with anti-HER2 therapy without chemotherapy.

PURPOSE: Anti-HER2 therapy delivered in the adjuvant setting for breast cancer is given in conjunction with cytotoxic chemotherapy. For HER2-positive (HER2+) patients who cannot tolerate chemotherapy, there is no randomized data regarding the role of anti-HER2 therapy without chemotherapy. METHODS: The National Cancer Database (NCDB) was queried for non-metastatic breast cancer patients with estrogen receptor-positive (ER+) and HER2+ breast cancer who received surgery and endocrine therapy, without chemotherapy from 2013 to 2016. Outcomes were compared between endocrine therapy alone (ET) or endocrine therapy with anti-HER2 therapy (ET + aHER2). Univariate and multivariate Cox-proportional hazards models were used to analyze the association between clinical characteristics and survival outcomes between groups. Propensity score matching (PSM) was performed to account for differences between the two groups. RESULTS: Of all patients with non-metastatic ER+/HER2+ breast cancer, we identified 9458 (20.5%) who did not receive chemotherapy. Of the 6741 patients who received ET, 17.2% also received aHER2 therapy. Median follow-up was 31.7 months (IQR 21.1-42.1). In the aHER2 group (vs. ET), there were more patients with older age, higher stage, node positivity, poorly or undifferentiated disease, lymphovascular invasion, lobular cancer, and Medicare insurance. Compared to the ET cohort, ET + aHER2 was not significantly associated with improved OS on multivariate analysis (HR 0.88 95% CI 0.68-1.15) or after propensity score matching (HR 0.80 95% CI 0.57-1.11). CONCLUSIONS: There is no significant difference in survival with the addition of HER2 therapy to endocrine therapy in ER+/HER2+ non-metastatic breast cancer patients who do not receive chemotherapy. To our knowledge, this is the largest series investigating this question.

Radiation Dose Reduction in Early-Stage Hodgkin Lymphoma.

INTRODUCTION: Treatment for early-stage Hodgkin lymphoma (HL) involves radiotherapy (RT), chemotherapy, or combined modality therapy (CMT). We analyzed reduction of RT dose in CMT, particularly in the context of German Hodgkin Study Group (GHSG) HD10 randomized trial results of 2010. PATIENTS AND METHODS: The National Cancer Data Base was queried for patients with stage I-II HL receiving CMT. RT dose and associated characteristics were analyzed. Stage I and absence of B symptoms were used as a surrogate for early-stage favorable disease. RESULTS: Of 31,301 patients with stage I-II HL, 11,457 received CMT between 2004 and 2015. Using the surrogate defined above, 1955 patients (17.1%) were classified as having favorable disease. The majority (61.6%) received 30-36 Gy, while 7.0% received 20 Gy. The provision of 20 Gy was more common in stage I patients (12.3% vs. 5.4% in stage II) and at academic facilities (10.8% vs. 6.3%-8.9% at other facilities). Use of 20 Gy (vs. 30-36 Gy) was less likely with thorax site (odds ratio [OR] 0.43 vs. head and neck), stage II disease (OR 0.41), and B symptoms (OR 0.33). Notably, the use of 20 Gy increased dramatically after 2010 (the year of publication of GHSG HD10 trial results), with rates of 12.3% in 2010-2015 versus 0.1% in 2004-2009 (OR 6.3, P < .001). This was even more pronounced in cases of favorable early-stage disease, with 25.5% after 2010 versus 2.8% before 2010 (OR 13.2, P < .001). The use of doses > 36 Gy decreased over a corresponding time period (OR 0.44, P < .001). CONCLUSION: Analysis of CMT for patients with early-stage HL demonstrates variability in RT dose, including increasing use of 20 Gy and decreasing use of high doses > 36 Gy.

Patterns of Care and Survival of Cutaneous Angiosarcoma of the Head and Neck.

OBJECTIVE: To analyze the patterns of care and survival of cutaneous angiosarcomas of the head and neck. STUDY DESIGN: Retrospective cohort study. SETTING: National Cancer Database. METHODS: The National Cancer Database was queried to select patients with cutaneous angiosarcoma of the head and neck between 2004 and 2015. For survival analysis, patients were included only if they received definitive treatment and complete data. Prognostic factors were analyzed by univariate and multivariable Cox regression. RESULTS: We identified 693 patients diagnosed with head and neck angiosarcomas during the study period. The majority were male (n = 489, 70.6%) and elderly (median, 77 years). A total of 421 patients (60.8%) met the criteria for survival analyses. These patients were treated with surgery and radiation (n = 178, 42.3%), surgery alone (n = 138, 32.8%), triple-modality therapy (n = 48, 11.4%), surgery and chemotherapy (n = 29, 6.9%), and chemoradiation (n = 28, 6.7%). With a median follow-up of 29 months, the 3-year survival was 50.1%. Patients undergoing surgery had better median survival than those who did not (38.1 vs 21.0 months, P = .04). Age, comorbidity, tumor size, and surgical margins were significant factors in univariate analyses. On multivariable analysis, age ≥75 years (hazard ratio, 2.65; 95% CI, 1.80-3.88; P < .001) and positive margins (hazard ratio, 1.91; 95% CI, 1.44-2.51; P < .001) predicted worse overall survival. CONCLUSION: Angiosarcoma of head and neck is a rare malignancy that affects the elderly. Surgical treatment with negative margins is associated with improved survival. Even with curative-intent multimodality treatment, the survival of patients aged ≥75 years is limited.

Ipsilateral breast tumor recurrence in early stage breast cancer patients treated with breast conserving surgery and adjuvant radiation therapy: Concordance of biomarkers and tumor location from primary tumor to in-breast tumor recurrence.

BACKGROUND: Patients with an in-breast tumor recurrence (IBTR) after breast-conserving therapy have a high risk of distant metastasis and disease-related mortality. Classifying clinical parameters that increase risk for recurrence after IBTR remains a challenge. AIM: To describe primary and recurrent tumor characteristics in patients who experience an IBTR and understand the relationship between these characteristics and disease outcomes. METHODS: Patients with stage 0-II breast cancer treated with lumpectomy and adjuvant radiation were identified from institutional databases of patients treated from 2003-2017 at our institution. Overall survival (OS), disease-free survival, and local recurrence-free survival (LRFS) were estimated using the Kaplan Meier method. We identified patients who experienced an isolated IBTR. Concordance of hormone receptor status and location of tumor from primary to recurrence was evaluated. The effect of clinical and treatment parameters on disease outcomes was also evaluated. RESULTS: We identified 2164 patients who met the eligibility criteria. The median follow-up for all patients was 3.73 [interquartile range (IQR) 2.27-6.07] years. Five-year OS was 97.7% (95%CI: 96.8%-98.6%) with 28 deaths; 5-year LRFS was 98.0% (97.2-98.8) with 31 IBTRs. We identified 37 patients with isolated IBTR, 19 (51.4%) as ductal carcinoma in situ and 18 (48.6%) as invasive disease, of whom 83.3% had an in situ component. Median time from initial diagnosis to IBTR was 1.97 (IQR: 1.03-3.5) years. Radiotherapy information was available for 30 of 37 patients. Median whole-breast dose was 40.5 Gy and 23 patients received a boost to the tumor bed. Twenty-five of thirty-two (78.1%) patients had concordant hormone receptor status, HER-2 receptor status, and estrogen receptor (ER) (P = 0.006) and progesterone receptor (PR) (P = 0.001) status from primary to IBTR were significantly associated. There were no observed changes in HER-2 status from primary to IBTR. The concordance between quadrant of primary to IBTR was 10/19 [(62.2%), P = 0.008]. Tumor size greater than 1.5 cm (HR = 0.44, 95%CI: 0.22-0.90, P = 0.02) and use of endocrine therapy upfront (HR = 0.36, 95%CI: 0.18-0.73, P = 0.004) decreased the risk of IBTR. CONCLUSION: Among patients with early stage breast cancer who had breast conserving surgery treated with adjuvant RT, ER/PR status and quadrant were highly concordant from primary to IBTR. Tumor size greater than 1.5 cm and use of adjuvant endocrine therapy were significantly associated with decreased risk of IBTR.

Survival of oral tongue squamous cell carcinoma in young adults.

BACKGROUND: Small cohort studies have suggested oral tongue squamous cell carcinoma (OTSCC) could be associated with worse prognosis in individuals younger than 40. METHODS: We compared the survival of all OTSCC cases in the National Cancer Database under 40 years old with those older than 40, excluding patients over 70. Cox regression and propensity score matched (PSM) survival analyses were performed. RESULTS: A total of 22 930 OTSCC patients were identified. The under 40 group consisted of 2566 (9.9%) cases; 20664 were 40 to 70 (90.1%). Most were male (13 713, 59.8%), stage I-II (12 754, 72.4%), and treated by surgery alone (13 973, 63.2%). Survival in patients under 40 was higher (79.6% vs 69.5%, P < .001). In PSM analysis (n = 2928) controlling for all 10 significant factors in multivariate regression, patients under 40 had a 9% higher 5-year survival (77.1% vs 68.2%, P < .001). CONCLUSION: Contrary to the prior reports, younger patients with OTSCC did not have worse survival in the National Cancer Database.

Dosimetric assessment of tumor control probability in intensity and volumetric modulated radiotherapy plans.

OBJECTIVE:: Radiobiological models have been used to calculate the outcomes of treatment plans based on dose-volume relationship. This study examines several radiobiological models for the calculation of tumor control probability (TCP) of intensity modulated radiotherapy plans for the treatment of lung, prostate, and head and neck (H&N) cancers. METHODS:: Dose volume histogram (DVH) data from the intensity modulated radiotherapy plans of 36 lung, 26 prostate, and 87 H&N cases were evaluated. The Poisson, Niemierko, and Marsden models were used to calculate the TCP of each disease group treatment plan. The calculated results were analyzed for correlation and discrepancy among the three models, as well as different treatment sites under study. RESULTS:: The median value of calculated TCP in lung plans was 61.9% (34.1-76.5%), 59.5% (33.5-73.9%) and 32.5% (0.0-93.9%) with the Poisson, Niemierko, and Marsden models, respectively. The median value of calculated TCP in prostate plans was 85.1% (56.4-90.9%), 81.2% (56.1-88.7%) and 62.5% (28.2-75.9%) with the Poisson, Niemierko, and Marsden models, respectively. The median value of calculated TCP in H&N plans was 94.0% (44.0-97.8%) and 94.3% (0.0-97.8%) with the Poisson and Niemierko models, respectively. There were significant differences between the calculated TCPs with the Marsden model in comparison with either the Poisson or Niemierko model (p < 0.001) for both lung and prostate plans. The TCPs calculated by the Poisson and Niemierko models were significantly correlated for all three tumor sites. CONCLUSION:: There are variations with different radiobiological models. Understanding of the correlation and limitation of a TCP model with dosimetric parameters can help develop the meaningful objective functions for plan optimization, which would lead to the implementation of outcome-based planning. More clinical data are needed to refine and consolidate the model for accuracy and robustness. ADVANCES IN KNOWLEDGE:: This study has tested three radiobiological models with varied disease sites. It is significant to compare different models with the same data set for better understanding of their clinical applicability.

Neoadjuvant chemotherapy in local-regionally advanced nasopharyngeal carcinoma: A National Cancer Database analysis.

OBJECTIVES/HYPOTHESIS: To assess patterns of care and outcomes with the use of neoadjuvant chemotherapy followed by definitive radiation in local-regionally advanced nasopharyngeal carcinoma. STUDY DESIGN: Retrospective database analysis. METHODS: We queried the National Cancer Database for patients with T3-4N2 or T1-4N3 nasopharyngeal carcinoma who received concurrent chemoradiotherapy or neoadjuvant chemotherapy followed by radiation. Overall survival (OS) was analyzed using the Kaplan-Meier method, propensity-score matching, and a Cox proportional hazards model adjusting for demographic and disease-specific prognostic factors. RESULTS: From 2004 to 2014, a total of 1,731 patients were identified, including 504 patients (27%) who received neoadjuvant chemotherapy. Neoadjuvant chemotherapy was used more frequently in years 2008 to 2010 (34%) and 2011 to 2014 (30%) compared with 2004 to 2007 (22%) (χ2 P = .001). At a median follow-up of 36.6 months, patients had 3-year OS of 66% in the neoadjuvant group compared with 70% in those who received concurrent chemoradiotherapy (log rank P = .29). On subgroup analysis by histology, T stage, and N stage, there remained no differences in OS between the two groups. On multivariable analysis, there was no significant survival difference associated with neoadjuvant chemotherapy (adjusted hazard ratio [HR]: 1.05, 95% confidence interval [CI]: 0.89-1.25, P = .54). In a propensity score-matched population of 1,008 patients (504 with neoadjuvant therapy and 504 without), there was no significant survival difference associated with neoadjuvant chemotherapy (H: 1.13, 95% CI: 0.93-1.38, P = .22). CONCLUSIONS: Neoadjuvant chemotherapy was used in over 25% of patients, and its use is increasing. However, neoadjuvant chemotherapy was not associated with any differences in survival compared to concurrent chemoradiotherapy. LEVEL OF EVIDENCE: 4 Laryngoscope, 128:2770-2777, 2018.

Post-mastectomy Radiation Therapy in Breast Cancer Patients with Nodal Micrometastases.

BACKGROUND: Recent data support the use of post-mastectomy radiation therapy (PMRT) in women with one to three positive lymph nodes; however, the benefit of PMRT in patients with micrometastatic nodal disease (N1mi) is unknown. We evaluated the survival impact of PMRT in patients with N1mi within the National Cancer Database. METHODS: The pattern of care and survival benefit of PMRT was examined in women with pT1-2N1mi breast cancer who underwent mastectomy without neoadjuvant chemotherapy. Univariable and multivariable Cox proportional hazard models were employed for survival analysis, and subanalyses of high-risk patients and a propensity score-matched (PSM) cohort were completed. RESULTS: From 2004 to 2014, we identified 14,019 patients who fitted the study criteria. PMRT was delivered in 18.5% of patients and its use increased over the study period. Patients treated with PMRT were younger, had better performance status and larger primaries, were estrogen receptor (ER)-negative, had higher grade, lymphovascular invasion and positive surgical margins, and more often received systemic therapy. PMRT was significantly associated with overall survival (OS) in univariable analysis (hazard ratio [HR] 0.75 [0.64-0.89]), but was not significant in multivariable analysis (adjusted HR 1.01 [0.84-1.20]). There was no survival benefit to PMRT in ER-negative, high-grade, and/or young patients. There were 2 (0.9%) death events in the sentinel lymph node biopsy (SLNB) + PMRT group versus 21 (2.9%) in the SLNB-alone group (log-rank p = 0.053), and 8 (3.9%) death events in the axillary lymph node biopsy (ALNB) + PMRT group versus 27 (3.6%) in the axillary lymph node dissection-alone group (p = 0.82). There was no significant association between PMRT and OS within the PSM subgroup. CONCLUSION: In this largest reported retrospective study, no OS differences were associated with PMRT, which suggests that PMRT may not benefit every patient with microscopic nodal disease.

Early Palliative Care for Patients With Brain Metastases Decreases Inpatient Admissions and Need for Imaging Studies.

BACKGROUND: Early encounters with palliative care (PC) can influence health-care utilization, clinical outcome, and cost. AIM: To study the effect of timing of PC encounters on brain metastasis patients at an academic medical center. SETTING/PARTICIPANTS: All patients diagnosed with brain metastases from January 2013 to August 2015 at a single institution with inpatient and/or outpatient PC records available for review (N = 145). DESIGN: Early PC was defined as having a PC encounter within 8 weeks of diagnosis with brain metastases; late PC was defined as having PC after 8 weeks of diagnosis. Propensity score matched cohorts of early (n = 46) and late (n = 46) PC patients were compared to control for differences in age, gender, and Karnofsky Performance Status (KPS) at diagnosis. Details of the palliative encounter, patient outcomes, and health-care utilization were collected. RESULTS: Early PC versus late PC patients had no differences in baseline KPS, age, or gender. Early PC patients had significantly fewer number of inpatient visits per patient (1.5 vs 2.9; P = .004), emergency department visits (1.2 vs 2.1; P = .006), positron emission tomography/computed tomography studies (1.2 vs 2.7, P = .005), magnetic resonance imaging scans (5.8 vs 8.1; P = .03), and radiosurgery procedures (0.6 vs 1.3; P < .001). There were no differences in overall survival (median 8.2 vs 11.2 months; P = .2). Following inpatient admissions, early PC patients were more likely to be discharged home (59% vs 35%; P = .04). CONCLUSIONS: Timely PC consultations are advisable in this patient population and can reduce health-care utilization.

The impact of adjuvant chemoradiotherapy timing on survival of head and neck cancers.

BACKGROUND: Delays in postoperative head and neck (HN) radiotherapy have been associated with decreased overall survival; however, the impact of delays in postoperative HN chemoradiotherapy remains undefined. METHODS: All patients with nonmetastatic HN cancer (oral cavity, oropharynx, larynx, hypopharynx) who underwent curative intent surgery and received adjuvant chemoradiotherapy were identified from the National Cancer Database (2005-2012). Overall treatment time (OTT) was defined as the time from surgery to the end of radiation therapy. Statistical methods included Cox proportional hazards modeling, which adjusted for clinicopathologic, demographic, and socioeconomic factors. Recursive partitioning analysis (RPA) identified the optimal threshold of OTT via conditional inference trees to estimate the greatest differences in overall survival (OS) on the basis of randomly selected training and validation sets. RESULTS: A total of 16,733 patients were included, with a median follow-up of 37 months. Median OS for OTT in a predefined threshold of ≤ 13 weeks was 10.1 years (95% confidence interval [CI], 9.8 years; not reached) compared with 8.7 years (95% CI, 8.2-9.2 years) in > 13 weeks. On multivariate analysis, OTT of > 13 weeks versus ≤ 13 weeks independently increased mortality risk (hazard ratio, 1.10; 95% CI, 1.04-1.17; P = < 0.001). RPA identified an optimal OTT threshold of 97 days (interquartile range: 96-98 days). The OTT threshold of 97 days was confirmed in a full Cox regression model estimating the risk of death according to overall treatment time as a continuous variable. CONCLUSION: In this large hospital-based national data, an OTT of greater than approximately 14 weeks most consistently increased the risk of death. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:2326-2332, 2018.

Utilization and Survival of Postoperative Radiation or Chemoradiation for pT1-2N1M0 Head and Neck Cancer.

Objective To analyze the patterns of care and survival for pT1-2N1M0 head and neck cancer based on receipt of surgery alone, surgery + postoperative radiotherapy (S + RT), or surgery + postoperative chemoradiotherapy (S + CRT). Study Design Retrospective analysis. Setting National Cancer Database. Subjects and Methods We queried the database for patients with stage pT1-2N1M0 squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx between 2004 and 2012 who were treated with surgery with negative margins and no extracapsular extension. Logistic regression was used to assess predictors of receipt of postoperative treatment. Overall survival was assessed by the Kaplan-Meier method, and Cox regression analysis identified covariates that affected it. Results There were 1598 patients included in this study: 566 (35.4%) received surgery alone; 726 (45.4%), S + RT; and 306 (19.1%), S + CRT. The 5-year overall survival was 68.8%, 74.0%, and 87.8%, respectively ( P = .009 comparing S + RT and surgery alone, P < .001 for all other comparisons). On multivariable logistic regression, academic centers were associated with a decreased likelihood of S + RT (odds ratio = 0.71) and S + CRT (odds ratio = 0.66). Multivariable Cox regression demonstrated no difference in survival for S + RT over surgery alone (hazard ratio = 0.88, 95% CI = 0.70-1.09, P = .24); however, there was a survival benefit associated with S + CRT (hazard ratio = 0.57, 95% CI = 0.39-0.81, P = .002). Conclusion Nearly 65% of patients with pT1-2N1 head and neck cancer with negative margins and no extracapsular extension received S + RT or S + CRT. Improvement in survival was noted only for patients who received S + CRT.

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.

Patterns of care and impact of brachytherapy boost utilization for squamous cell carcinoma of the base of tongue in a large, national cohort.

PURPOSE: The National Cancer Data Base was analyzed to evaluate the patterns of care and impact of brachytherapy (BT) boost on overall survival (OS) for patients with squamous cell carcinoma of the base of tongue. METHODS AND MATERIALS: Patients with nonmetastatic squamous cell carcinoma of the base of tongue between 2004 and 2012 who received concurrent external beam radiation therapy (EBRT) and chemotherapy with or without BT boost in the definitive setting were queried. Overall survival was assessed by the Kaplan-Meier method. Cox regression analysis was used to identify covariates that affected OS. RESULTS: There were 15,934 patients included in this study; 137 (0.9%) received EBRT + BT and the remaining received EBRT only. Median followup was 41.2 months. The utilization of BT boost declined from 2.1% in 2004 to 0.2% in 2012 (p < 0.0001), whereas intensity-modulated radiation therapy use increased from 22.8% in 2004 to 69.2% in 2012 (p < 0.0001). The three- and 5-year OS was 83.2% and 78.3% for patients receiving EBRT + BT compared with 77.4% and 69.0% for those receiving EBRT only (p = 0.03). The difference in survival was significantly better among patients with T3-4 tumors with EBRT + BT boost (p = 0.009) however, there was no survival benefit among patients with T1-2 tumors (p = 0.72). The analysis was repeated with patients who received intensity-modulated radiation therapy vs. EBRT with BT boost and the survival difference was sustained only for those with T3-4 tumors (p = 0.02). CONCLUSIONS: Brachytherapy boost has decreased in its utilization even though it was associated with favorable survival outcomes particularly among patients with higher T-stage tumors.

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.

DNA Methylation-Based Classifier for Accurate Molecular Diagnosis of Bone Sarcomas.

PURPOSE: Pediatric sarcomas provide a unique diagnostic challenge. There is considerable morphologic overlap between entities, increasing the importance of molecular studies in the diagnosis, treatment, and identification of therapeutic targets. We developed and validated a genome-wide DNA methylation based classifier to differentiate between osteosarcoma, Ewing's sarcoma, and synovial sarcoma. MATERIALS AND METHODS: DNA methylation status of 482,421 CpG sites in 10 Ewing's sarcoma, 11 synovial sarcoma, and 15 osteosarcoma samples were determined using the Illumina Infinium HumanMethylation450 array. We developed a random forest classifier trained from the 400 most differentially methylated CpG sites within the training set of 36 sarcoma samples. This classifier was validated on data drawn from The Cancer Genome Atlas (TCGA) synovial sarcoma, TARGET Osteosarcoma, and a recently published series of Ewing's sarcoma. RESULTS: Methylation profiling revealed three distinct patterns, each enriched with a single sarcoma subtype. Within the validation cohorts, all samples from TCGA were accurately classified as synovial sarcoma (10/10, sensitivity and specificity 100%), all but one sample from TARGET-OS were classified as osteosarcoma (85/86, sensitivity 98%, specificity 100%) and 14/15 Ewing's sarcoma samples classified correctly (sensitivity 93%, specificity 100%). The single misclassified osteosarcoma sample demonstrated high EWSR1 and ETV1 expression on RNA-seq although no fusion was found on manual curation of the transcript sequence. Two additional clinical samples, that were difficult to classify by morphology and molecular methods, were classified as osteosarcoma when previously suspected to be a synovial sarcoma and Ewing's sarcoma on initial diagnosis, respectively. CONCLUSION: Osteosarcoma, synovial sarcoma, and Ewing's sarcoma have distinct epigenetic profiles. Our validated methylation-based classifier can be used to provide diagnostic assistance when histological and standard techniques are inconclusive.