Prognostic factors for pediatric, adolescent, and young adult patients with non-DIPG grade 4 gliomas: a contemporary pooled institutional experience.

PURPOSE: WHO grade 4 gliomas are rare in the pediatric and adolescent and young adult (AYA) population. We evaluated prognostic factors and outcomes in the pediatric versus AYA population. METHODS: This retrospective pooled study included patients less than 30 years old (yo) with grade 4 gliomas treated with modern surgery and radiotherapy. Overall survival (OS) and progression-free survival (PFS) were characterized using Kaplan-Meier and Cox regression analysis. RESULTS: Ninety-seven patients met criteria with median age 23.9 yo at diagnosis. Seventy-seven patients were ≥ 15 yo (79%) and 20 patients were < 15 yo (21%). Most had biopsy-proven glioblastoma (91%); the remainder had H3 K27M-altered diffuse midline glioma (DMG; 9%). All patients received surgery and radiotherapy. Median PFS and OS were 20.9 months and 79.4 months, respectively. Gross total resection (GTR) was associated with better PFS in multivariate analysis [HR 2.00 (1.01-3.62), p = 0.023]. Age ≥ 15 yo was associated with improved OS [HR 0.36 (0.16-0.81), p = 0.014] while female gender [HR 2.12 (1.08-4.16), p = 0.03] and DMG histology [HR 2.79 (1.11-7.02), p = 0.029] were associated with worse OS. Only 7% of patients experienced grade 2 toxicity. 62% of patients experienced tumor progression (28% local, 34% distant). Analysis of salvage treatment found that second surgery and systemic therapy significantly improved survival. CONCLUSION: Age is a significant prognostic factor in WHO grade 4 glioma, which may reflect age-related molecular alterations in the tumor. DMG was associated with worse OS than glioblastoma. Reoperation and systemic therapy significantly increased survival after disease progression. Prospective studies in this population are warranted.

Early and Midtreatment Mortality in Palliative Radiotherapy: Emphasizing Patient Selection in High-Quality End-of-Life Care.

BACKGROUND: Palliative radiotherapy (RT) is effective, but some patients die during treatment or too soon afterward to experience benefit. This study investigates end-of-life RT patterns to inform shared decision-making and facilitate treatment consistent with palliative goals. MATERIALS AND METHODS: All patients who died ≤6 months after initiating palliative RT at an academic cancer center between 2015 and 2018 were identified. Associations with time-to-death, early mortality (≤30 days), and midtreatment mortality were analyzed. RESULTS: In total, 1,620 patients died ≤6 months from palliative RT initiation, including 574 (34%) deaths at ≤30 days and 222 (14%) midtreatment. Median survival was 43 days from RT start (95% CI, 41-45) and varied by site (P<.001), ranging from 36 (head and neck) to 53 days (dermal/soft tissue). On multivariable analysis, earlier time-to-death was associated with osseous (hazard ratio [HR], 1.33; P<.001) and head and neck (HR, 1.45; P<.001) sites, multiple RT courses ≤6 months (HR, 1.65; P<.001), and multisite treatments (HR, 1.40; P=.008), whereas stereotactic technique (HR, 0.77; P<.001) and more recent treatment year (HR, 0.82; P<.001) were associated with longer survival. No difference in time to death was noted among patients prescribed conventional RT in 1 to 10 versus >10 fractions (median, 40 vs 47 days; P=.272), although the latter entailed longer courses. The 30-day mortality group included 335 (58%) inpatients, who were 27% more likely to die midtreatment (P=.031). On multivariable analysis, midtreatment mortality among these inpatients was associated with thoracic (odds ratio [OR], 2.95; P=.002) and central nervous system (CNS; OR, 2.44; P=.002) indications, >5-fraction courses (OR, 3.27; P<.001), and performance status of 3 to 4 (OR, 1.63; P=.050). Conversely, palliative/supportive care consultation was associated with decreased midtreatment mortality (OR, 0.60; P=.045). CONCLUSIONS: Earlier referrals and hypofractionated courses (≤5-10 treatments) should be routinely considered for palliative RT indications, given the short life expectancies of patients at this stage in their disease course. Providers should exercise caution for emergent thoracic and CNS indications among inpatients with poor prognoses due to high midtreatment mortality.

Contemporary prostate cancer treatment choices in multidisciplinary clinics referenced to national trends.

BACKGROUND: The purpose of this study was to assess treatment choices among men with prostate cancer who presented at The University of Texas MD Anderson Cancer Center multidisciplinary (MultiD) clinic compared with nationwide trends. METHODS: In total, 4451 men with prostate cancer who presented at the MultiD clinic from 2004 to 2016 were analyzed. To assess nationwide trends, the authors analyzed 392,710 men with prostate cancer who were diagnosed between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. The primary endpoint was treatment choice as a function of pretreatment demographics. RESULTS: Univariate analyses revealed similar treatment trends in the MultiD and SEER cohorts. The use of procedural forms of definitive therapy decreased with age, including brachytherapy and prostatectomy (all P < .05). Later year of diagnosis/clinic visit was associated with decreased use of definitive treatments, whereas higher risk grouping was associated with increased use (all P < .001). Patients with low-risk disease treated at the MultiD clinic were more likely to receive nondefinitive therapy than patients in SEER, whereas the opposite trend was observed for patients with high-risk disease, with a substantial portion of high-risk patients in SEER not receiving definitive therapy. In the MultiD clinic, African American men with intermediate-risk and high-risk disease were more likely to receive definitive therapy than white men, but for SEER the opposite was true. CONCLUSIONS: Presentation at a MultiD clinic facilitates the appropriate disposition of patients with low-risk disease to nondefinitive strategies of patients with high-risk disease to definitive treatment, and it may obviate the influence of race.

Adjuvant combined-modality therapy for stage IIIC endometrioid and non-endometrioid endometrial cancer.

OBJECTIVE: To identify the optimal adjuvant treatment regimen for patients with endometrioid and non-endometrioid node-positive endometrial cancer. METHODS: We retrospectively identified 249 women with FIGO 2009 stage IIIC endometrial cancer at our institution who underwent surgical staging from 1985 to 2015 followed by external beam radiotherapy (RT), chemotherapy (CT), or a combination of CT + RT. Survival rates were calculated using the Kaplan-Meier method. RESULTS: The 5-year disease-specific survival (DSS) rate for all patients was 65%. Adjuvant CT + RT conferred higher rates of 5-year DSS as compared to CT alone in patients with grade 3 endometrioid and non-endometrioid tumors (61% vs. 27%, P = 0.04 and 67% vs. 38%, P = 0.02, respectively). Among patients with non-endometrioid tumors, treatment with concurrent chemoradiotherapy followed by additional sequential chemotherapy had higher 5-year DSS rates than with concurrent chemoradiotherapy alone (74% vs. 50%, P = 0.02). The 3-year pelvic recurrence rate was 5% with RT ±â€¯CT and 35% with CT alone (P < 0.001) for all patients. No paraaortic nodal failures were observed following extended-field RT, but 14% of patients who received pelvic-only RT or CT alone developed recurrences in the paraaortic nodes (P < 0.001). CONCLUSIONS: Combined-modality therapy including adjuvant external beam pelvic radiotherapy yields excellent outcomes for patients with all subtypes of node-positive endometrial cancer. The most pronounced DSS advantage from adjuvant chemoradiotherapy was evident in women with non-endometrioid endometrial cancer.

Radical prostatectomy or radiotherapy for high- and very high-risk prostate cancer: a multidisciplinary prostate cancer clinic experience of patients eligible for either treatment.

OBJECTIVE: To compare radical prostatectomy (RP) vs radiotherapy (RT) with androgen-deprivation therapy (ADT) in the setting of patients with high-risk and very high-risk (VHR) prostate cancer who were deemed eligible for either therapy and made a treatment choice after consultation in a multidisciplinary prostate cancer clinic (MDPCC), and to compare the MDPCC patients' outcomes to a matched Surveillance, Epidemiology and End Results (SEER) cohort. PATIENTS AND METHODS: Prospectively collected, retrospective study comparing patients who underwent RP (231 patients) vs RT+ADT (73) from 2004 to 2013. Biochemical recurrence (BCR), local recurrence, distant metastasis failure, and overall survival (OS) were calculated for each treatment group overall and according to National Comprehensive Cancer Network risk strata. A propensity score matched comparison with a SEER cohort was performed for OS. RESULTS: There was no difference in local recurrence (hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.0-7.9; P = 0.06), distant metastasis failure (HR 2.5, 95% CI 0.8-7.8; P = 0.1) and OS (HR 1.35, 95% CI 0.4-4.8; P = 0.6) between patients undergoing RP vs RT+ADT. Patients treated via the MDPCC survived on average 16.9 months (95% CI 13.1-20.8) longer than those in the matched SEER cohort. CONCLUSIONS: Long-term outcomes appear similar amongst patients with high-risk and VHR prostate cancer deemed eligible for either RP or RT, and treated after consultation in a MDPCC. Outcomes of the MDPCC patients were superior to those of the matched SEER cohort.

Pre-treatment neutrophil/lymphocyte ratio and platelet/lymphocyte ratio are prognostic of progression in early stage classical Hodgkin lymphoma.

To determine whether pre-treatment neutrophil/lymphocyte (NLR) or platelet/lymphocyte ratios (PLR) are predictive for progression in early-stage classical Hodgkin lymphoma (cHL), we derived NLR and PLR values for 338 stage I/II cHL patients and appropriate cut-off point values to define progression. Two-year freedom from progression (FFP) for patients with NLR ≥6·4 was 82·2% vs. 95·7% with NLR <6·4 (P < 0·001). Similarly, 2-year FFP was 84·3% for patients with PLR ≥266·2 vs. 96·1% with PLR <266·2 (P = 0·003). On univariate analysis, both NLR and PLR were significantly associated with worse FFP (P = 0·001). On multivariate analysis, PLR remained a significant, independent prognostic factor (P < 0·001).

Treatment at a high-volume centre is associated with improved survival among patients with non-metastatic hepatocellular carcinoma.

BACKGROUND & AIMS: The association between case volume and outcomes is well-documented for several cancer types. However, it is unknown if patients with hepatocellular carcinoma treated at high-volume centres have improved overall survival. METHODS: About 135 442 patients diagnosed with hepatocellular carcinoma between 2004-2014 were identified in the Commission on Cancer's National Cancer Database and 53 795 patients were excluded for metastatic or node-positive disease. Average annual case volume was calculated as the total number of cases treated per centre from 2004-2014 and dividing by 10. Receiver operating characteristic curves showed the most significant case number threshold between high-volume centres and remaining centres. Univariate and multivariate analyses were performed using Cox regression analysis to determine factors associated with improved survival. Kaplan-Meier curves and log-rank tests were used for overall survival estimates. RESULTS: A total of 81 647 patients with stage I-III hepatocellular carcinoma were treated at a total of 1218 centres. The median [range] case volume per year averaged over the 10-year study period was 48.6 [0.1-205.5]. High-volume centres treated >114 cases of hepatocellular carcinoma annually while remaining centre treated ≤114 cases. Median survival for patients treated in high-volume centres and remaining centres were 31.9 and 16.6 months respectively (Log Rank P < .001). On multivariate analysis, average annual case volume was significantly associated with improved survival. CONCLUSIONS: Receiving treatment at a high-volume centre is significantly associated with survival for patients with non-metastatic disease. Improved survival at high-volume centres may be related to access to a variety of treatment modalities, multidisciplinary evaluation, and/or subspecialty expertise.

Role of Radiation Therapy in the Multidisciplinary Management of Uterine Carcinosarcoma.

OBJECTIVES: This study aimed to evaluate the impact of radiation therapy on outcomes for patients with uterine carcinosarcoma (UC). METHODS/MATERIALS: We retrospectively reviewed the records of 155 women with stage I (98), II (11), or III (46) UC who underwent total abdominal hysterectomy/bilateral salpingo-oophorectomy at our institution between 1990 and 2011. Survival rates were assessed using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression analyses were performed. RESULTS: Seventy-six patients (49%) received radiation therapy: 38 (50%) had vaginal cuff brachytherapy (VBT) alone and 38 had external beam radiation therapy (EBRT) ± VBT. Seventy patients (45%) received chemotherapy (12 concurrent, 49 adjuvant, 9 both). The 5-year overall survival rate was 48.6% (stage I, 53.8%; II, 30.0%; and III, 42.5%). The disease-specific survival (DSS) rate was 57.2% (stage I, 60.9%; II, 44.4%; and III, 51.8%). Patients treated with EBRT had a higher 5-year pelvic disease control rate (88.3%) than did patients treated with VBT only (67.4%) or no radiation (71.2%; P = 0.04). In stage III patients, EBRT was associated with higher 5-year pelvic disease control (90.0% vs 55.5%, P = 0.046), DSS (64.6% vs 46.4%, P = 0.13), and overall survival (64.6% vs 34.0%, P = 0.04) rates. For all 155 patients, age at least 65 years, cervical involvement, and lymph vascular space invasion were correlated with lower DSS on univariate and multivariate analyses. In addition, treatment with concurrent chemoradiation therapy was independently associated with a higher DSS rate on multivariate analysis. CONCLUSIONS: Patients with UC have a high rate of relapse in the regional nodes and distant sites. External beam radiation therapy improves locoregional control in all stages and may improve survival in stage III patients who are at the highest risk of pelvic relapse.

Perirenal Adiposity is Associated With Lower Progression-Free Survival From Ovarian Cancer.

OBJECTIVES: Abdominal obesity is linked with a higher risk of developing ovarian cancer. However, the link between abdominal obesity and survival after diagnosis of ovarian cancer is unknown. The purpose of this study was to determine the impact of abdominal obesity on progression-free survival in patients with ovarian cancer. METHODS: Among 258 patients, visceral and subcutaneous adipose tissue volume, along with perirenal adipose tissue thickness (a visceral adiposity proxy measure) was retrospectively measured from abdominal computed tomography (CT) scans obtained within 6 months of ovarian cancer diagnosis. Progression-free survival was computed using the Kaplan-Meier method and log-rank tests. Univariate and multivariate Cox proportional hazards analysis was used to determine relationships between measures of abdominal obesity and clinical variables in relation to progression-free survival. RESULTS: Patients with perirenal adipose tissue thickness greater than 5 mm(median) had lower rates of progression-free survival at 5 years compared with patients with perirenal adipose tissue thickness less than 5 mm (45.6% vs 53.8%, respectively). Perirenal adipose tissue thickness less than 5 mm was associated with lower rates of progression-free survival on multivariate analysis (hazard ratio = 1.37; 95% confidence interval, 1.03-1.82). There was no correlation with other metrics of abdominal adiposity on progression-free survival in univariate or multivariate analysis. CONCLUSIONS: Our data suggest that perirenal adipose, but not body mass index, visceral, or subcutaneous fat volume that were measured within 6 months from diagnosis, is associated with lower rates of progression-free survival in ovarian cancer.

A multi-institutional analysis of peritransplantation radiotherapy in patients with relapsed/refractory Hodgkin lymphoma undergoing autologous stem cell transplantation.

BACKGROUND: No consensus exists regarding the use of radiotherapy (RT) in conjunction with high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) for patients with relapsed/refractory classical Hodgkin lymphoma (HL). The objectives of the current study were to characterize practice patterns and assess the efficacy and toxicity of RT at 2 major transplantation centers. METHODS: Eligible patients underwent HDC/ASCT from 2006 through 2015 using the combination of either carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) or cyclophosphamide, BCNU, and etoposide (CBV). RESULTS: For the cohort of 189 patients, the 4-year overall survival rate was 80%, the progression-free survival rate was 67%, and the local control (LC) rate was 68%. RT was used within 4 months of ASCT for 22 patients (12%) and was given more often for disease that was early stage, primary refractory, or [18 F]fluorodeoxyglucose (FDG)-avid at the time of HDC/ASCT. Disease recurrence occurring after HDC/ASCT was associated with primary refractory disease and FDG-avidity at the time of HDC/ASCT. RT was not found to be associated with LC, progression-free survival, or overall survival on univariate analysis. In a model incorporating primary refractory HL and FDG-avid disease at the time of HDC/ASCT, RT was found to be associated with a decreased risk of local disease recurrence (hazard ratio, 0.3; P = .02). In patients with primary refractory HL and/or FDG-avid disease at the time of HDC/ASCT, the 4-year LC rate was 81% with RT versus 49% without RT (P = .03). There was one case of Common Terminology Criteria for Adverse Events grade ≥ 3 RT-related toxicity (acute grade 3 pancytopenia). CONCLUSIONS: In patients undergoing ASCT for relapsed/refractory HL, peritransplantation RT was used more often for disease that was early stage, primary refractory, or FDG-avid after salvage conventional-dose chemotherapy. RT was associated with improved LC of high-risk localized disease and was well tolerated with modern techniques. Cancer 2017;123:1363-1371. © 2016 American Cancer Society.

7-year follow-up after stereotactic ablative radiotherapy for patients with stage I non-small cell lung cancer: Results of a phase 2 clinical trial.

BACKGROUND: The authors evaluated the efficacy, patterns of failure, and toxicity of stereotactic ablative radiotherapy (SABR) for patients with medically inoperable, clinical stage I non-small cell lung cancer (NSCLC) in a prospective clinical trial with 7 years of follow-up. Clinical staging was performed according to the seventh edition of the American Joint Committee on Cancer TNM staging system. METHODS: Eligible patients with histologically confirmed NSCLC of clinical stage I as determined using positron emission tomography staging were treated with SABR (50 grays in 4 fractions). The primary endpoint was progression-free survival. Patients were followed with computed tomography and/or positron emission tomography/computed tomography every 3 months for the first 2 years, every 6 months for the next 3 years, and then annually thereafter. RESULTS: A total of 65 patients were eligible for analysis. The median age of the patients was 71 years, and the median follow-up was 7.2 years. A total of 18 patients (27.7%) developed disease recurrence at a median of 14.5 months (range, 4.3-71.5 months) after SABR. Estimated incidences of local, regional, and distant disease recurrence using competing risk analysis were 8.1%, 10.9%, and 11.0%, respectively, at 5 years and 8.1%, 13.6%, and 13.8%, respectively, at 7 years. A second primary lung carcinoma developed in 12 patients (18.5%) at a median of 35 months (range, 5-67 months) after SABR. Estimated 5-year and 7-year progression-free survival rates were 49.5% and 38.2%, respectively; the corresponding overall survival rates were 55.7% and 47.5%, respectively. Three patients (4.6%) experienced grade 3 treatment-related adverse events. No patients developed grade 4 or 5 adverse events (toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]). CONCLUSIONS: With long-term follow-up, the results of the current prospective study demonstrated outstanding local control and low toxicity after SABR in patients with clinical stage I NSCLC. Regional disease recurrence and distant metastases were the dominant manifestations of failure. Surveillance for second primary lung carcinoma is recommended. Cancer 2017;123:3031-39. © 2017 American Cancer Society.

Addition of Definitive Radiotherapy to Chemotherapy in Patients With Newly Diagnosed Metastatic Nasopharyngeal Cancer.

Background: Management of metastatic (M1) nasopharyngeal cancer (NPC) is controversial; data suggest high overall survival (OS) rates with definitive chemoradiotherapy (CRT). Herein, we evaluated OS in patients with M1 NPC undergoing chemotherapy alone versus CRT. Methods: The National Cancer Data Base was queried for M1 NPC cases. Patients undergoing no/unknown chemotherapy and/or with unknown/nondefinitive radiotherapy (RT) doses (<60 Gy) were excluded. Logistic regression analysis ascertained clinical factors associated with RT administration. Kaplan-Meier analysis evaluated OS between both cohorts; Cox proportional hazards modeling assessed factors associated with OS. Survival was then evaluated between matched populations using inverse-probability-weighted regression adjustment. OS between groups was also measured in patients surviving ≥1 and ≥3 years to address bias from poor-prognostic subsets (eg, widely disseminated disease), and those receiving CRT ≤30 and ≤60 days of each other (surrogates for concurrent CRT) versus >30 and >60 days (sequential) of each other. Results: Of 555 patients, 296 (53%) received chemotherapy alone and 259 (47%) underwent CRT. Patients undergoing CRT more often had private insurance (P=.001) and lived in areas with higher education levels (P=.028). Median OS in the chemotherapy-only and CRT cohorts were 13.7 and 25.8 months, respectively (P<.001); differences persisted between matched populations (P<.001). On multivariate analysis, receipt of additional RT independently predicted for improved OS (P<.001). OS differences between cohorts remained apparent when evaluating patients surviving for ≥1 (P<.001) and ≥3 (P=.002) years. Patients who received concurrent or sequential CRT displayed improved OS over those receiving chemotherapy alone, for both the 30-day (P<.001) and 60-day cutoffs (P<.001). Conclusions: Patients with M1 NPC undergoing definitive RT and chemotherapy experienced higher survival than those receiving chemotherapy alone. Risk stratification and patient selection for such combined modality interventions is critical.

Variation in insurance status by patient demographics and tumor site among nonelderly adult patients with cancer.

BACKGROUND: In the United States, an estimated 48 million individuals live without health insurance. The purpose of the current study was to explore the Variation in insurance status by patient demographics and tumor site among nonelderly adult patients with cancer. METHODS: A total of 688,794 patients aged 18 to 64 years who were diagnosed with one of the top 25 incident cancers (representing 95% of all cancer diagnoses) between 2007 and 2010 in the Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Patient characteristics included age, race, sex, marital status, and rural or urban residence. County-level demographics included percent poverty level. Insurance status was defined as having non-Medicaid insurance, Medicaid coverage, or no insurance. RESULTS: On multivariate logistic regression analyses, younger age, male sex, nonwhite race, being unmarried, residence in counties with higher levels of poverty, and rural residence were associated with being uninsured versus having non-Medicaid insurance (all P <.001). The highest rates of non-Medicaid insurance were noted among patients with prostate cancer (92.3%), melanoma of the skin (92.5%), and thyroid cancer (89.5%), whereas the lowest rates of non-Medicaid insurance were observed among patients with cervical cancer (64.2%), liver cancer (67.9%), and stomach cancer (70.9%) (P <.001). Among uninsured individuals, the most prevalent cancers were lung cancer (14.9%), colorectal cancer (12.1%), and breast cancer (10.2%) (P <.001). Lung cancer caused the majority of cancer mortality in all insurance groups. CONCLUSIONS: Rates of insurance coverage vary greatly by demographics and by cancer type. The expansion of health insurance coverage would be expected to disproportionally benefit certain demographic populations and cancer types.

Management of nodal recurrences of endometrial cancer with IMRT.

OBJECTIVE: Pelvic and paraortic lymph nodal regions are frequent sites of relapse in women with endometrial cancer who have not undergone adjuvant external beam radiation. We investigated outcomes after definitive management of nodal relapses of endometrial cancer with intensity modulated radiation therapy (IMRT). METHODS: Between 2002-2012, 38 patients with endometrial cancer who had no prior external beam radiation were treated definitively using IMRT for regionally confined pelvic or paraortic nodal recurrences. Thirteen (34%) had chemotherapy prior to radiation, and 21 (55%) received concurrent chemotherapy. The nodal basins were typically treated to 45-50Gy, with a boost to the gross tumor to a median total of 64.7Gy (range 59-73Gy). RESULTS: The median overall survival from date of recurrence was 46.1months and the 2-year survival was 71%. Patients who received concurrent chemotherapy had a significantly longer median survival (61.9months versus 28.7months, p=0.034). In-field failures were more frequent in patients who received chemotherapy prior to radiation, had a shorter recurrence-free interval, received a lower radiation dose, and had higher tumor grade. Three patients (8%) experienced grade 3-4 late gastrointestinal (GI) toxicity. CONCLUSIONS: Long-term survival can be achieved in women with nodal recurrences of endometrial cancer. The use of concurrent chemotherapy and dose escalation with IMRT as feasible may improve survival for women with isolated nodal recurrences of endometrial cancer.

Factors associated with local-regional failure after definitive chemoradiation for locally advanced esophageal cancer.

BACKGROUND: Locally advanced esophageal cancer is often treated with a trimodality approach. While a substantial proportion of such patients initially achieve a clinical complete response (cCR) after chemoradiation, only a small proportion achieve durable control. We analyzed patients who reached cCR after definitive chemoradiation for esophageal cancer to identify clinical predictors of local disease recurrence. METHODS: We identified 141 patients who obtained initial cCR after definitive chemoradiation without surgery for esophageal cancer from 2002 through 2009. The initial response to treatment was assessed by endoscopic evaluation and biopsy results, with cCR defined as having no evidence of disease present. Patterns of failure were categorized as in-field (within the planned treatment volume [PTV]), outside the radiation treatment field, or both. RESULTS: At a median follow-up of 22 months (range, 6-87 months), 77 patients (55 %) had experienced disease recurrence (local or both). Of first failures, 32 (23 %) were outside the radiation field, followed by 30 (21 %) within the field, and 15 (11 %) were both. By multivariate analysis, in-field failure after cCR was associated with a pretreatment standardized uptake value on positron emission tomography of >10 (subhazard ratio [SHR] 3.31, p = 0.023) and poorly differentiated tumors (SHR 3.69, p = 0.031). All failures, in-field and out-of-field, correlated with non-Caucasian ethnicity (SHR 2.55, p = 0.001), N1 disease (SHR 2.05, p = 0.034), T3/T4 disease (SHR 3.56, p = 0.011), and older age (SHR 0.96, p = 0.008). CONCLUSIONS: Our data suggest that selected clinical characteristics can be used to predict failure patterns after definitive chemoradiation. Such risk-assessment strategies can help individualize therapy.

Outcomes and predictive factors for salvage therapy after local--regional recurrence following neoadjuvant chemotherapy and breast conserving therapy.

BACKGROUND: There are few data addressing local-regional recurrence (LRR) and salvage therapies in patients treated with neoadjuvant chemotherapy (NCT) compared to those treated with surgery first. We characterize the clinical course and predictive features of salvage treatment for LRR after breast conserving therapy (BCT) analyzed by initial treatment. METHODS: We identified 1,589 patients who underwent BCT; 1,141 (72 %) patients underwent initial surgery, and 448 (28 %) received NCT. Kaplan-Meier and Cox regression analyses were performed to analyze factors associated with overall survival (OS), local control (LC) of recurrence, and distant metastasis-free survival (DMFS) following LRR. RESULTS: 56 patients had a LRR, for a crude recurrence rate of 3 %. For patients with potentially curable recurrence (excluding distant metastases within 3 months of LRR), the 5-year OS, LC, and DMFS rates were 52, 77, and 69 %. On multivariate analysis, initial pathologically negative node status and use of surgery for salvage were significant factors associated with higher OS. Additionally, older age was associated with higher LC rates after salvage. Estrogen receptor-positive disease and surgery for LRR were associated with reduced risk of distant metastases; regional recurrence and use of initial adjuvant chemotherapy were associated with increased risk of distant metastases. For each of these endpoints, the addition of NCT to the multivariate model did not approach significance. CONCLUSIONS: LRR is an uncommon event after BCT and many patients with LRR remain curable (5-year OS >50 %). Our data indicate that NCT does not compromise salvage after LRR, providing further assurance that this strategy is safe for appropriately selected breast cancer patients.

Galectin-7 levels predict radiation response in squamous cell carcinoma of the cervix.

OBJECTIVE: We previously found that galectin-7 was upregulated in patients with cervical cancer who remained recurrence-free after chemoradiation. We hypothesized that pretreatment levels of galectin-7 predict radiation response in patients with squamous cell carcinoma (SCC) of the cervix. METHODS: Galectin-7 expression was assessed by immunohistochemical staining of a tissue microarray of paraffin-embedded specimens from 161 patients with cervical SCC treated with definitive radiation therapy in 1980-1999. Galectin-7 expression was scored as absent or present. Distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were computed using the Kaplan-Meier method and log-rank tests. RESULTS: The median age at diagnosis was 45 years (range 21-85) and median follow-up interval was 71 months (range 0-285). Of the 161 patients, 105 (65%) had FIGO stage IB disease, 18 (11%) stage IIA, and 38 (24%) stage IIB. Median tumor diameter was 5.5 cm (range 3.5-8). Seven patients (4%) received concurrent chemotherapy; 139 patients (86%) had galectin-7-positive tumors and 22 (14%) galectin-7-negative tumors. Five-year DMFS rates for patients with galectin-7-positive versus -negative tumors were 73% and 55% (p=0.05); DSS, 65% and 36% (p=0.004); and OS, 64% and 36% (p=0.005). In multivariate analysis adjusting for age, stage, and tumor diameter, galectin-7 expression remained a significant predictor of DMFS (hazard ratio [HR]=0.43, p=0.03), DSS (HR=0.34, p=0.001), and OS (HR=0.34, p=0.001). CONCLUSIONS: Elevated galectin-7 expression is associated with improved outcomes after radiation therapy for cervical cancer. Further studies are required to validate these findings and clarify the role of galectin-7 in disease progression and radiation response.

Supratentorial gross-totally resected non-anaplastic ependymoma: population based patterns of care and outcomes analysis.

Observation following gross-total resection (GTR) for non-anaplastic supratentorial ependymomas is often advocated based on small, retrospective series. The purpose of this study is to perform a population-based analysis to examine outcomes for this rare cohort of low-risk patients. A retrospective analysis was conducted utilizing the Surveillance, Epidemiology and End Results Program of the United States National Cancer Institute. We identified patients with supratentorial non-anaplastic ependymoma who underwent GTR alone or GTR followed by radiation. We identified 92 patients who met these criteria. The median age was 17.5 years (range 1-83) with the majority female (58 %) and white (75 %). Radiotherapy (RT) was delivered in half of patients. The 5-/10-year Kaplan-Meier estimated overall survival (OS) and cause-specific survival (CSS) for the overall cohort was 83.2/71.4 and 84.1/78.0 %, respectively. There was no evidence of decreased CSS (HR 0.52 [0.18-1.51]; p = 0.23) or OS (HR 0.63 [0.25-1.59]; p = 0.33) with the omission of RT on univariate analysis. Age ≥18 years correlated with worse OS (HR 4.01 [1.45-11.11]; p = 0.008) and CSS (HR 2.86 [0.99-8.31]; p = 0.05). RT did not impact outcome for this low-risk cohort of patients. Older age correlates with poor prognosis.

Stereotactic body radiation therapy for management of spinal metastases in patients without spinal cord compression: a phase 1-2 trial.

BACKGROUND: Spinal stereotactic body radiation therapy (SBRT) is increasingly used to manage spinal metastases, yet the technique's effectiveness in controlling the symptom burden of spinal metastases has not been well described. We investigated the clinical benefit of SBRT for managing spinal metastases and reducing cancer-related symptoms. METHODS: 149 patients with mechanically stable, non-cord-compressing spinal metastases (166 lesions) were given SBRT in a phase 1-2 study. Patients received a total dose of 27-30 Gy, typically in three fractions. Symptoms were measured before SBRT and at several time points up to 6 months after treatment, by the Brief Pain Inventory (BPI) and the M D Anderson Symptom Inventory (MDASI). The primary endpoint was frequency and duration of complete pain relief. The study is completed and is registered with ClinicalTrials.gov, number NCT00508443. FINDINGS: Median follow-up was 15·9 months (IQR 9·5-30·3). The number of patients reporting no pain from bone metastases, as measured by the BPI, increased from 39 of 149 (26%) before SBRT to 55 of 102 (54%) 6 months after SBRT (p<0·0001). BPI-reported pain reduction from baseline to 4 weeks after SBRT was clinically meaningful (mean 3·4 [SD 2·9] on the BPI pain-at-its-worst item at baseline, 2·1 [2·4] at 4 weeks; effect size 0·47, p=0·00076). These improvements were accompanied by significant reduction in opioid use during the first 6 months after SBRT (43 [28·9%] of 149 patients with strong opioid use at baseline vs 20 [20·0%] of 100 at 6 months; p=0·011). Ordinal regression modelling showed that patients reported significant pain reduction according to the MDASI during the first 6 months after SBRT (p=0·00003), and significant reductions in a composite score of the six MDASI symptom interference with daily life items (p=0·0066). Only a few instances of non-neurological grade 3 toxicities occurred: nausea (one event), vomiting (one), diarrhoea (one), fatigue (one), dysphagia (one), neck pain (one), and diaphoresis (one); pain associated with severe tongue oedema and trismus occurred twice; and non-cardiac chest pain was reported three times. No grade 4 toxicities occurred. Progression-free survival after SBRT was 80·5% (95% CI 72·9-86·1) at 1 year and 72·4% (63·1-79·7) at 2 years. INTERPRETATION: SBRT is an effective primary or salvage treatment for mechanically stable spinal metastasis. Significant reductions in patient-reported pain and other symptoms were evident 6 months after SBRT, along with satisfactory progression-free survival and no late spinal cord toxicities. FUNDING: National Cancer Institute of the US National Institutes of Health.

A prospective phase 2 study of surgery followed by chemotherapy and radiation for superior sulcus tumors.

BACKGROUND: The optimal treatment for locally advanced superior sulcus tumors is not clear. The authors report long-term results of a trial examining the safety and efficacy of surgery followed by concurrent chemoradiation therapy for this disease. METHODS: Thirty-two patients with resectable or marginally resectable superior sulcus tumors at The University of Texas MD Anderson Cancer Center from 1994 to 2010 were enrolled in a prospective trial. Surgery involved segmentectomy or lobectomy with en bloc resection of the involved chest wall and complete nodal staging; radiation therapy (RT) began 14 to 42 days later to a dose of 60 grays (Gy) in 50 1.2-Gy fractions if surgical margins were negative or 64.8 Gy in 54 1.2-Gy fractions if margins were positive. Two cycles of etoposide (50 mg/m(2) ) and cisplatin (50 mg/m(2) ) were given during RT, and another 3 cycles were given after RT. Eleven patients underwent prophylactic cranial irradiation (PCI). RESULTS: The protocol completion rate was 78%. Gross total resection was accomplished in all 32 patients; 28% underwent R1 resection. Operative mortality was 0%. The most common surgical complication was postoperative pneumonia (25%). At a median follow-up time of 53.4 months (range, 2-154 months), the 2-year, 5-year, and 10-year rates of locoregional control were 84%, 76%, and 76%; distant metastasis-free survival, 52%, 48%, and 48%; disease-free survival, 49%, 45%, and 45%; and overall survival, 72%, 50%, and 45%, respectively. The brain was the most common site of distant failure (n = 5), but no patient who received PCI experienced brain metastasis. CONCLUSIONS: Surgery followed by postoperative chemoradiation is safe and effective for the treatment of marginally resectable superior sulcus tumors.