Analyses of prognosis-related factors of intracranial solitary fibrous tumors and hemangiopericytomas help understand the relationship between the two sorts of tumors

Increasing evidence has suggested a close relationship between solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) in the central nervous system (CNS). However, CNS SFTs differentiate from HPCs in their clinical behavior and patient prognoses. Analyses of prognosis-related factors can help clarify the relationship between SFT and HPC. The intracranial SFT and HPC cases treated in our departments from January 2002 to December 2012 were retrospectively reviewed. The SFT and HPC cases were also combined into an SFT/HPC group. The factors associated with patient progression-free survival (PFS) and overall survival (OS) were statistically analyzed using uni- and multivariate analyses. Fifty-eight intracranial SFT/HPC patients including 38 SFT patients and 20 HPC patients were treated during this period. The “Marseille grading” evaluated upon the histological aggressive phenotypes was applied in this study. The grading reflected a malignant progression ranging from “conventional” SFTs (grade I) to WHO III HPCs (grade III), and grade was negatively correlated with the PFS and OS of the SFT, HPC and SFT/HPC patients (P?<?0.05).The multivariate analyses revealed that gross total resection (GTR) was significantly positively correlated with PFS and OS in the SFT, HPC and SFT/HPC patients and that radiotherapy was significantly positively correlated with PFS in the HPC and SFT/HPC patients (P?<?0.05). In conclusion, the intracranial SFTs and HPCs share common prognostic factors including extent of surgery and pathology, moreover, the histological grading of the aggressive phenotypes supports the unifying of the CNS SFT and HPC into one tumor entity of SFT/HPC.     

Multifactorial,site‐specific recurrence model after radical cystectomy for urothelial carcinoma

BACKGROUND:

A scoring algorithm of site‐specific disease recurrence after cystectomy for urothelial carcinoma was designed.

METHODS:

Identified were 1388 patients who underwent radical cystectomy for nonmetastatic urothelial carcinoma between 1980 and 1998. Clinical, surgical, and pathologic features were evaluated for associations with 4 locations of site‐specific disease recurrence: upper urinary tract, abdomen/pelvis, thoracic region, and bone. Recurrence‐free survival rates were estimated using the Kaplan‐Meier method. Cox proportional hazards models were fit to test associations with disease recurrence.

RESULTS:

A total of 493 (35.5%) patients experienced at least 1 recurrence. There were 67, 388, 143, and 145 patients with recurrences to the upper tract, abdomen/pelvis, thoracic region, and bone at a median of 3.1 years, 1.1 years, 1.3 years, and 1.0 years, respectively. Pathologic T4 stage (hazard ratio [HR], 2.84; P = .006), positive ureteral margins (HR, 5.71; P < .001), and multifocality (HR, 2.07; P = .009) were found to be independent predictors of upper tract recurrence. Pathologic T3 (HR, 2.30; P < .001) and T4 stage (HR, 3.55; P < .001), lymph node invasion (HR, 1.97; P < .001), extent of lymphadenectomy (pNx [HR, 1.66; P = .002] and <10 lymph nodes [HR, 1.52; P < .001]), multifocality (HR, 1.80; P < .001), and prostatic involvement (HR, 1.45; P = .019) were found to be independent predictors of abdominal/pelvic recurrence. Features independently associated with thoracic recurrence included pathologic T3 (HR, 2.61; P < .001) and T4 (HR, 3.39; P < .001), lymph node invasion (HR, 2.64; P < .001), extent of lymphadenectomy (pNx [HR, 1.89; P = .019] and <10 lymph nodes [HR, 1.58; P < .030]), and multifocality (HR, 1.79; P < .001). Pathologic T3 (HR, 3.45; P < .001) and T4 stage (HR, 3.87; P < .001), lymph node invasion (HR, 1.79; P = .006), occupational exposure to radiation (HR, 2.97; P = .003), and a positive urethral margin (HR, 2.28; P = .039) were found to be independent predictors of osseous recurrence. Macroscopic hematuria (HR, 0.52; P = .009) and obesity (HR, 0.59; P = .027) were found to be protective and negatively associated with upper tract and osseous recurrence, respectively. Scoring algorithms to predict the likelihood of disease recurrence to these sites were developed using regression coefficients from the multivariable models.

CONCLUSIONS:

Scoring algorithms based on independent predictors of site‐specific recurrence were presented. These models may be used to tailor postoperative surveillance to the individual patient based upon clinicopathologic features at the time of cystectomy. Cancer 2010. © 2010 American Cancer Society.     

Age at diagnosis and the utility of prognostic testing in patients with chronic lymphocytic leukemia

BACKGROUND:

A study was undertaken to analyze the survival of chronic lymphocytic leukemia (CLL) patients relative to age‐matched individuals in the general population and determine the age‐stratified utility of prognostic testing.

METHODS:

All 2487 patients diagnosed with CLL between January 1995 and June 2008 and cared for in the Mayo Clinic Division of Hematology were categorized by age at diagnosis and evaluated for differences in clinical characteristics, time to first treatment, and overall survival (OS).

RESULTS:

Among Rai stage 0 patients, survival was shorter than the age‐matched general population for patients aged <55 years (P < .001), 55 to 64 years (P < .001), and 65 to 74 years (P < .001), but not those aged ≥75 years at diagnosis (P = not significant). CD38, IGHV mutation, and ZAP‐70 each predicted time to first treatment independent of stage for all age groups (all P < .04), but had less value for predicting OS, particularly as age increased. IGHV and fluorescent in situ hybridization (FISH) predicted OS independent of stage for patients aged <55 years (P ≤ .001), 55 to 64 years (P ≤ .004), and 65 to 74 years (P ≤ .001), but not those aged ≥75 years. CD38 and ZAP‐70 each predicted OS independent of stage for only 2 of 4 age categories. Among Rai 0 patients aged <75 years, survival was shorter than the age‐matched population only for IGHV unmutated (P < .001) patients or those with unfavorable FISH (P < .001).

CONCLUSIONS:

Survival of CLL patients aged <75 years is shorter than the age‐matched general population regardless of disease stage. Among patients aged <75 years, the simple combinations of stage and IGHV or stage and FISH identifies those with excess risk of death relative to the age‐matched population. Although useful for predicting time to first treatment independent of stage for patients of all ages, prognostic testing had little utility for predicting OS independent of stage among patients aged ≥75 years. Cancer 2010. © 2010 American Cancer Society.     

Prognostic factors and predictive model in patients with advanced biliary tract adenocarcinoma receiving first‐line palliative chemotherapy

BACKGROUND:

Advanced biliary tract adenocarcinoma (BTA) has been a rare but fatal cancer. If unresectable, palliative chemotherapy improved the quality and length of life, but to the authors' knowledge, prognostic factors in such patients have not been well established to date. In the current study, prognostic factors were investigated in patients with advanced BTA receiving first‐line palliative chemotherapy.

METHODS:

Data from 213 patients with advanced BTA who were in prospective phase 2 or retrospective studies from September 2000 through October 2007 were used.

RESULTS:

With a median follow‐up duration of 29.7 months, the median overall survival (OS) was 7.3 months (95% confidence interval [95% CI], 6.3 months‐8.3 months). A Cox proportional hazards model indicated that metastatic disease (hazards ratio [HR], 1.521; P = .011), intrahepatic cholangiocellular carcinoma (HR, 1.368; P = .045), liver metastasis (HR, 1.845; P < .001), Eastern Cooperative Oncology Group performance status (HR, 1.707; P < .001), and alkaline phosphatase level (IU/L) (HR, 1.001; P < .001) were statistically significant independent predictors of poor prognosis. Patients were classified into 3 risk groups based on the prognostic index (PI), which was constructed using the regression coefficients of each variable. The median OS was 11.5 months (95% CI, 9.6 months‐13.5 months) for the low‐risk group (PI ≤ 1.5; n = 67), 7.3 months (95% CI, 5.7 months‐8.9 months) for the intermediate‐risk group (PI > 1.5 but ≤ 2.2; n = 75), and 3.6 months (95% CI, 2.9 months‐4.1 months) for the high‐risk group (PI > 2.2; n = 70 [P < .001]).

CONCLUSIONS:

Five prognostic factors in patients with advanced BTA were identified. The predictive model based on PI appears to be promising and may be used for the management of individual patients and to guide the design of future clinical trials, although external validation is needed. Cancer 2009. © 2009 American Cancer Society.     

Prognostic model to predict outcomes in nonsmall cell lung cancer patients treated with gefitinib as a salvage treatment

BACKGROUND:

A prognostic model based on clinical parameters for nonsmall cell lung cancer (NSCLC) patients treated with gefitinib (250 mg/day) as a salvage therapy was devised.

METHODS:

Clinical data regarding a total of 316 metastatic or recurrent NSCLC patients who were treated with gefitinib were analyzed.

RESULTS:

Poor prognostic factors for overall survival (OS) by multivariate analysis were an Eastern Cooperative Oncology Group (ECOG) performance status of 2 to 3 (hazards ratio [HR] of 2.07; 95% confidence interval [CI], 1.57‐2.73 [P < .001]), the presence of intra‐abdominal metastasis (HR of 1.76; 95% CI, 1.33‐2.34 [P < .001]), elevated serum alkaline phosphatase (HR of 1.50; 95% CI, 1.13‐2.00 [P = .005]), time interval from diagnosis to gefitinib therapy of ≤12 months (HR of 1.48; 95% CI, 1.12‐1.95 [P = .005]), low serum albumin (HR of 1.45; 95% CI, 1.09‐1.92 [P = .009]), progression‐free interval for previous chemotherapy of ≤12 weeks (HR of 1.40; 95% CI, 1.0‐1.84 [P = .015]), white blood cell >10,000/μL (HR of 1.38; 95% CI, 1.02‐1.85 [P = .032]), and ever‐smoker (HR of 1.33; 95% CI, 1.02‐1.75 [P = .033]). Of the 272 patients applicable to this prognostic model, 41 patients (15%) were categorized as a good prognosis group (0‐1 risk factors), 100 patients (37%) as an intermediate prognosis group (2‐3 risk factors), 81 patients (30%) as a poor prognosis group (4‐5 risk factors), and 50 patients (16%) as a very poor prognosis group (≥6 risk factors). The median OS from the time of gefitinib treatment for the good, intermediate, poor, and very poor prognosis groups were 18.0 months, 11.2 months, 4.0 months, and 1.3 months, respectively (P < .001).

CONCLUSIONS:

This prognostic model based on easily available clinical variables would be useful to identify patients who might derive more benefit from gefitinib treatment and to make decisions in clinical practice. Cancer 2009. © 2009 American Cancer Society.     

Pemetrexed in combination with cisplatin versus cisplatin monotherapy in patients with recurrent or metastatic head and neck cancer: Final results of a randomized, double-blind, placebo-controlled, phase 3 study

BACKGROUND:

Recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) is associated with poor survival. Platinum‐based chemotherapy is often a first‐line treatment. Pemetrexed has shown single‐agent activity in SCCHN and in combination with cisplatin for other tumors. This trial examined the efficacy of pemetrexed‐cisplatin for SCCHN.

METHODS:

In a double‐blind phase 3 trial, patients with recurrent or metastatic SCCHN and no prior systemic therapy for metastatic disease were randomized to pemetrexed (500 mg/m²) plus cisplatin (75 mg/m²; n = 398) or placebo plus cisplatin (75 mg/m²; n = 397) to assess overall survival (OS) and secondary endpoints.

RESULTS:

Median OS was 7.3 months in the pemetrexed‐cisplatin arm and 6.3 months in the placebo‐cisplatin arm (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.75‐1.02; P = .082). Median progression‐free survival (PFS, months) was similar in both treatment arms (pemetrexed‐cisplatin, 3.6; placebo‐cisplatin, 2.8; HR, 0.88; 95% CI, 0.76‐1.03; P = .166). Among patients with performance status 0 or 1, pemetrexed‐cisplatin (n = 347) led to longer OS and PFS than placebo‐cisplatin (n = 343; 8.4 vs 6.7 months; HR, 0.83; P = .026; 4.0 vs 3.0 months; HR, 0.84; P = .044, respectively). Among patients with oropharyngeal cancers, pemetrexed‐cisplatin (n = 86) resulted in longer OS and PFS than placebo‐cisplatin (n = 106; 9.9 vs 6.1 months; HR, 0.59; P = .002; 4.0 vs 3.4 months; HR, 0.73; P = .047, respectively). Pemetrexed‐cisplatin toxicity was consistent with studies in other tumors.

CONCLUSIONS:

Pemetrexed‐cisplatin compared with placebo‐cisplatin did not significantly improve survival for the intent‐to‐treat population. However, in a prespecified subgroup analysis, pemetrexed‐cisplatin showed OS and PFS advantage for patients with performance status 0 or 1 or oropharyngeal cancers. Cancer 2012. © 2012 American Cancer Society.     

The role of postoperative radiotherapy for the treatment of gangliogliomas

BACKGROUND:

Because of their rarity, no prospective studies have been performed regarding gangliogliomas. The optimal treatment regimen is unclear. In this study, the authors compared 4 therapies for local control (LC) and overall survival (OS) in patients with ganglioglioma.

METHODS:

In 402 patients with ganglioglioma, outcomes were compared for patients who underwent gross total resection alone (GTR) (n = 188), GTR plus radiotherapy (GTR + RT) (n = 21), subtotal resection alone (STR) (n = 113), and STR plus RT (STR + RT (n = 80). Age, sex, tumor site, and histologic grade also were investigated. Subgroup analyses were performed for both low‐grade and high‐grade tumors.

RESULTS:

The 10‐year LC rates were 89% after GTR, 90% after GTR + RT, 52% after STR, and 65% after STR + RT (P < .001); and the 10‐year OS rates were 95%, 95%, 62%, and 74%, respectively (P < .001). After STR, irradiation significantly improved LC (P = .004) but not OS (P = .22). After GTR, irradiation did not significantly improve LC (P = .23) or OS (P = .29). On multivariate analyses, LC and OS were associated with therapy and pathologic grade, and OS also was associated with tumor site. In low‐grade tumors, STR + RT resulted in better LC (P = .016) but not better OS (P = .18); and, after GTR, LC (P = .28) and OS (P = 1.0) were not improved with postoperative radiotherapy. In high‐grade tumors, STR + RT resulted in better LC (P = .016) but not better OS (P = .41); after GTR, LC (P = .56) and OS (P = .61) were not improved with irradiation.

CONCLUSIONS:

According to this review, GTR should be performed whenever safely possible and does not require postoperative irradiation. If only STR is achieved, then RT improves LC of both low‐grade and high‐grade tumors and, thus, should be considered seriously. Cancer 2010. © 2010 American Cancer Society.     

The impact of socioeconomic status on stage of cancer at diagnosis and survival

BACKGROUND:

Lower socioeconomic status (SES) is associated with worsened cancer survival. The authors evaluate the impact of SES on stage of cancer at diagnosis and survival in Ontario, Canada.

METHODS:

All incident cases of breast, colon, rectal, nonsmall cell lung, cervical, and laryngeal cancer diagnosed in Ontario during the years 2003‐2007 were identified by using the Ontario Cancer Registry. Stage information is captured routinely for patients seen at Ontario's 8 Regional Cancer Centers (RCCs). The Ontario population was divided into quintiles (Q1‐Q5) based on community median household income reported in the 2001 census; Q1 represents the poorest communities. Overall survival (OS) and cancer‐specific survival (CSS) were determined with Kaplan‐Meier methodology. A Cox model was used to evaluate the association between survival and SES, stage, and age.

RESULTS:

Stage at diagnosis was available for 38,431 of 44,802 (85%) of cases seen at RCCs. The authors observed only very small differences in stage distribution by SES. Across all cases in Ontario, the authors found substantial gradients in 5‐year OS and 3‐year CSS across Q1 and Q5 for breast (7% absolute difference in OS, P < .001; 4% CSS, P < .001), colon (8% OS, P < .001; 3% CSS, P = .002), rectal (9% OS, P < .001; 4% CSS, P = .096), nonsmall cell lung (3% OS, P = .002; 2% CSS, P = .317), cervical (16% OS, P < .001; 10% CSS, P = .118), and laryngeal cancers (1% OS, P = .045; 3% CSS, P = .011). Adjustments for stage and age slightly diminished the survival gradient only among patients with breast cancer.

CONCLUSIONS:

Despite universal healthcare, SES remains associated with survival among patients with cancer in Ontario, Canada. Disparities in outcome were not explained by differences in stage of cancer at time of diagnosis. Cancer 2010. © 2010 American Cancer Society.     

Outcomes of radical nephroureterectomy: A series from the Upper Tract Urothelial Carcinoma Collaboration

BACKGROUND:

The literature on upper tract urothelial carcinoma (UTUC) has been limited to small, single center studies. A large series of patients treated with radical nephroureterectomy for UTUC were studied, and variables associated with poor prognosis were identified.

METHODS:

Data on 1363 patients treated with radical nephroureterectomy at 12 academic centers were collected. All pathologic slides were re‐reviewed by genitourinary pathologists according to strict criteria.

RESULTS:

Pathologic review revealed renal pelvis location (64%), necrosis (21.6%), lymphovascular invasion (LVI) (24.8%), concomitant carcinoma in situ (28.7%), and high‐grade disease (63.7%). A total of 590 patients (43.3%) underwent concurrent, lymphadenectomy and 135 (9.9%) were lymph node (LN) ‐positive. Over a mean follow‐up of 51 months, 379 (28%) patients experienced disease recurrence outside of the bladder and 313 (23%) died of UTUC. The 5‐year recurrence‐free and cancer‐specific survival probabilities (±SD) were 69% ± 1% and 73% ± 1%, respectively. On multivariate analysis, high tumor grade (hazards ratio [HR]: 2.0, P < .001), advancing pathologic T stage (P‐for‐trend <.001), LN metastases (HR: 1.8, P < .001), infiltrative growth pattern (HR: 1.5, P < .001), and LVI (HR: 1.2, P = .041) were associated with disease recurrence. Similarly, patient age (HR: 1.1, P = .001), high tumor grade (HR: 1.7, P = .001), increasing pathologic T stage (P‐for‐trend <.001), LN metastases (HR: 1.7, P < .001), sessile architecture (HR: 1.5, P = .002), and LVI (HR: 1.4, P = .02) were independently associated with cancer‐specific survival.

CONCLUSIONS:

Radical nephroureterectomy provided durable local control and cancer‐specific survival in patients with localized UTUC. Pathologic tumor grade, T stage, LN status, tumor architecture, and LVI were important prognostic variables associated with oncologic outcomes, which could potentially be used to select patients for adjuvant systemic therapy. Cancer 2009. © 2009 American Cancer Society.     

Intracranial hemangiopericytoma: clinical experience and treatment considerations in a modern series of 40 adult patients

INTRODUCTION:

Intracranial hemangiopericytoma (HPC) is a malignant meningothelial tumor. Because of its rarity, few guidelines exist for optimal management.

METHODS:

University of California at San Francisco patients managed for intracranial HPC were compiled into a single database based on a retrospective review of patient records. Univariate and multivariate regression was performed to determine factors that independently predicted treatment outcomes.

RESULTS:

A total of 40 patients with intracranial HPC were treated from 1989 to 2010. Treatment and follow‐up information was available for analysis on 35 patients. The median survival for all patients was 16.2 years after date of diagnosis, with 1‐year, 5‐year, and 10‐year survival rates of 100%, 92%, and 68%, respectively. Nineteen patients (54%) had HPC recurrence. The median time until recurrence was 5 years, with 1‐year, 5‐year, and 10‐year progression‐free survival rates of 96%, 49%, and 28%, respectively. Seven patients (20%) developed extracranial metastasis. Tumor characteristics associated with earlier recurrence included size ≥6 cm (log‐rank, P < .05) and nonskull base location (log‐rank, P < .05). Strategies combining adjuvant radiation with tumor resection appeared to hinder tumor progression, but had no effect on overall survival or the development of metastasis. Greater extent of resection was associated with increased overall survival (log‐rank, P < .05).

CONCLUSIONS:

Adjuvant radiation may show promise in preventing tumor progression, but recurrence remains a common treatment outcome regardless of initial strategy. When safe and feasible, gross total resection should be pursued as an initial surgical strategy to maximize overall survival. The propensity of these tumors to metastasize makes detailed staging imaging necessary. Cancer 2011;. © 2011 American Cancer Society.     

Prognostic factors for recurrent breast cancer patients with an isolated,limited number of lung metastases and implications for pulmonary metastasectomy

BACKGROUND:

The aim of this study was to evaluate the clinical treatment outcomes of recurrent breast cancer with a limited number of isolated lung metastases, and to evaluate the role of pulmonary metastasectomy.

METHODS:

The authors consecutively enrolled 140 recurrent breast cancer patients with isolated lung metastasis from 1997 to 2007 in Seoul National University Hospital and retrospectively analyzed 45 patients who had <4 metastatic lesions.

RESULTS:

Fifteen patients had pulmonary metastasectomy followed by systemic treatment (pulmonary metastasectomy group), and 30 received systemic treatment alone (nonpulmonary metastasectomy group). The 3‐year progression‐free survival (PFS) and 4‐year overall survival (OS) was significantly longer in the pulmonary metastasectomy group than in the nonpulmonary metastasectomy group (3‐year PFS, 55.0% vs 4.5%, P < .001; 4‐year OS, 82.1% vs 31.6%, P = .001). In multivariate analysis, a disease‐free interval (DFI) of <24 months (hazard ratio [HR], 4.53; 95% CI, 1.72‐11.90), no pulmonary metastasectomy (HR, 9.52; 95% CI, 3.34‐27.18) and biologic subtypes such as human epithelial growth factor receptor‐2 positive (HR, 3.00; 95% CI, 1.04‐8.64) and triple negative (HR, 3.92; 95% CI, 1.32‐11.59) were independent prognostic factors for shorter PFS.

CONCLUSIONS:

The authors' results demonstrated that DFI and biologic subtypes of tumor are firm, independent, prognostic factors for survival, and pulmonary metastasectomy can be a reasonable treatment option in this population. Further prospective studies are warranted to evaluate the role of pulmonary metastasectomy. Cancer 2010. © 2010 American Cancer Society.     

Tumor recurrence and malignant progression of gangliogliomas

BACKGROUND.

Most gangliogliomas (GGs) are benign tumors, but tumor recurrence and malignant progression are observed in some patients.

METHODS.

The authors analyzed their experience with 4 recurrent/progressive GGs (World Health Organization [WHO] grade I), 21 tumors with atypical features (WHO grade II), and 5 tumors with anaplastic histologic features (WHO grade III). Histopathologic findings (23 patients) were reviewed. The mean follow‐up was 5.9 years (median, 4.5 years; range, 0.5‐14.7 years).

RESULTS.

The 5‐year survival rates were only 79% for patients who had tumors with atypical features and 53% for patients who had WHO grade III tumors. Secondary glioblastomas were diagnosed in 5 of 11 patients (45%) who underwent surgery for tumor recurrence. Age at surgery <40 years (P = .007) was associated significantly with better overall survival (OS), but it was not associated with better progression‐free survival (PFS). Clinical presentation (drug‐resistant epilepsy vs all other patients with seizures vs no seizures) was associated significantly with better OS (P = .005) and PFS (P < .001). Patients who had extratemporal tumors had a significantly shorter PFS (P = .01) but not OS. A complete resection was correlated strongly with both OS (P = .002) and PFS (P = .001). Neuropathologic examination revealed the presence of a gemistocytic cell component (PFS, P = .025), a lack of protein droplets (OS, P = .04; PFS, P = .05), and focal tumor cell‐associated CD34 immunolabeling (OS, P = .03) as significant predictors of an adverse clinical course.

CONCLUSIONS.

The current data supported a 3‐tiered GG histopathologic grading system that included an intermediate diagnostic category (atypical GG, WHO grade II). Careful attention to histopathologic findings and clinical parameters usually will identify patients who are at risk for an adverse clinical course. Cancer 2008. © 2008 American Cancer Society.     

Primary cardiac lymphoma: an analysis of presentation, treatment, and outcome patterns

BACKGROUND:

Primary cardiac lymphoma (PCL) represents a rare subset of non‐Hodgkin lymphoma, characterized by poor outcomes. The authors aimed to construct a framework of known clinical presentations, diagnostic features, disease complications, treatment, and outcomes to improve prognostication.

METHODS:

Individual patient data were obtained from defined cases of PCL (1949‐2009) and systematically analyzed.

RESULTS:

The authors report results of a review of 197 cases of PCL, with half of all cases reported since 1995. Survival was affected by 4 factors: immune status, left ventricular involvement, presence of extra‐cardiac disease, and arrhythmia. Median overall survival (OS) for immunocompromised and immunocompetent was 3.5 months (m) and not reached, respectively (HR 0.29, 95% CI, 0.13‐0.68; P = .004). LV involvement was uncommon (26%) and associated with an OS of only 1m, whereas patients free of LV involvement had a median OS of 22m (HR 0.28, 95% CI, 0.12‐0.64; P = .002). Patients with extracardiac disease had shorter median OS compared with those without (6m vs 22m, HR 0.49, 95% CI, 0.26‐0.91; P = .02). Those patients with an arrhythmia of any type had a median OS that was not reached (n = 55), whereas those without rhythm disturbances (n = 41) had median OS of 6m (HR 0.51, 95% CI, 0.29‐0.91; P = .024). Overall response rate to therapy was 84%, with long‐term OS over 40%.

CONCLUSIONS:

The current study presents the largest analysis of PCL to date. The data demonstrate that PCL is now more frequently diagnosed premortem and appears to have reasonable response rates. Lack of LV involvement and the presence of arrhythmias are associated with improved survival. Cancer 2011. © 2010 American Cancer Society.     

Ethnic and racial differences in patients with Ewing sarcoma

BACKGROUND:

Ewing sarcoma (ES) was a malignant tumor of bone or soft tissue. One of the few risk factors for developing ES is race, with a higher incidence noted in populations of European rather than African or Asian ancestry. The goal of the current study was to evaluate racial and ethnic differences in presentation and overall survival (OS) among patients diagnosed with ES before age 40 years.

METHODS:

Data from the Surveillance, Epidemiology, and End Results database identified 1715 patients aged <40 years who were diagnosed with ES between 1973 and 2005. Racial and ethnic group differences were compared using chi‐square tests. OS was estimated by Kaplan‐Meier analysis and compared using log‐rank tests and Cox models.

RESULTS:

Black patients had significantly more soft‐tissue tumors compared with white non‐Hispanic patients (P <.0001). Asian and white Hispanic patients were found to have an intermediate frequency of soft‐tissue tumors that also differed from white non‐Hispanic patients (P <.0001). White Hispanic patients presented with a higher proportion of larger tumors compared with white non‐Hispanic patients (P = .042). Black patients tended to be older than white non‐Hispanic patients (P = .012). Sex, frequency of pelvic tumors, and metastatic status did not appear to differ by ethnicity or race. OS was found to differ according to race and ethnicity. Even after controlling for known confounders, OS was significantly worse for black, Asian, and white Hispanic patients compared with white non‐Hispanic patients (P = .0031, P = .0182, and P = .0051, respectively).

CONCLUSIONS:

Ethnic and racial differences in characteristics and outcomes of patients with ES do exist. Understanding the etiology of these differences will require further study. Cancer 2010. © 2010 American Cancer Society.     

Carcinoma of the upper urinary tract

BACKGROUND:

Carcinomas of the upper urinary tract are uncommon tumors that usually occurred in elderly patients. Competing causes of mortality should be considered when treating these patients.

METHODS:

All patients with upper urinary tract tumors who were treated surgically at Centre Hospitalier Universitaire de Québec and affiliated hospitals from 1978 to 2001 were retrospectively reviewed. Clinical and pathologic variables were assessed from both the preoperative and postoperative periods of management, and clinical outcomes were tracked. Competing risks regression, Cox proportional hazards modeling, and multiple imputation were used to assess predictors of cancer‐related and competing risks?related mortality in both preoperative and postoperative settings.

RESULTS:

Competing risks were responsible for 46% of deaths in this cohort of 168 patients. Preoperatively, the most important predictor of cancer‐related mortality was a clinically invasive tumor (hazards ratio [HR], 3.97; P < .001), whereas increasing age (HR, 1.07; P < .001) was found to be the most important predictor of competing mortality. Postoperatively, tumor grade was the most important predictor of cancer‐related mortality (HR, 3.92; P < .001) whereas constitutional symptoms (HR, 1.91; P = .015) and increasing age (HR, 1.06; P < .001) were found to be predictive of competing mortality.

CONCLUSIONS:

In the current study, stage and grade were found to be the 2 most important independent predictors of survival in patients with tumors of the upper urinary tract and were highly correlated. Pain or weight loss was found to be a novel predictor of survival in this cancer. Although a survival disadvantage was not noted for women, nephron‐sparing surgery, ureteral tumors, or older patients with respect to cancer, competing causes of mortality were found to be responsible for greater than one‐third of observed deaths and age was the best predictor of this occurrence. Cancer 2009. © 2009 American Cancer Society.     

The long‐term outcome of treated high‐risk nonmuscle‐invasive bladder cancer

BACKGROUND:

The treatment of high‐risk nonmuscle‐invasive bladder cancer (NMIBC) is difficult given its unpredictable natural history and patient comorbidities. Because current case series are mostly limited in size, the authors report the outcomes from a large, single‐center series.

METHODS:

The authors reviewed all patients with primary, high‐risk NMIBC at their institution from 1994 to 2010. Outcomes were matched with clinicopathologic data. Patients who had muscle invasion within 6 months or had insufficient follow‐up (<6 months) were excluded. Correlations were analyzed using multivariable Cox regression and log‐rank analysis (2‐sided; P < .05).

RESULTS:

In total, 712 patients (median age, 73.7 years) were included. Progression to muscle invasion occurred in 110 patients (15.8%; 95% confidence interval [CI], 13%‐18.3%) at a median of 17.2 months (interquartile range, 8.9‐35.8 months), including 26.5% (95% CI, 22.2%‐31.3%) of the 366 patients who had >5 years follow‐up. Progression was associated with age (hazard ratio [HR], 1.04; P = .007), dysplastic urothelium (HR, 1.6; P = .003), urothelial cell carcinoma variants (HR, 3.2; P = .001), and recurrence (HR, 18.3; P < .001). Disease‐specific mortality occurred in 134 patients (18.8%; 95% CI, 16.1%‐21.9%) at a median of 28 months (interquartile range, 15‐45 months), including 28.7% (95% CI, 24.5%‐33.3%) of those who had 5 years of follow‐up. Disease‐specific mortality was associated with age (HR, 1.1; P < .001), stage (HR, 1.7; P = .003), dysplasia (HR, 1.3; P = .05), and progression (HR, 5.2; P < .001). Neither progression nor disease‐specific mortality were associated with the receipt of bacillus Calmette‐Guerin (P > .6).

CONCLUSIONS:

Within a program of conservative treatment, progression of high‐risk NMIBC was associated with a poor prognosis. Surveillance and bacillus Calmette‐Guerin were ineffective in altering the natural history of this disease. The authors concluded that the time has come to rethink the paradigm of management of this disease. Cancer 2012. © 2012 American Cancer Society.     

Expression patterns of Bmi-1 and p16 significantly correlate with overall, disease-specific, and recurrence-free survival in oropharyngeal squamous cell carcinoma

BACKGROUND:

The objective of this study was to link expression patterns of B‐cell–specific Moloney murine leukemia virus integration site 1 (Bmi‐1) and p16 to patient outcome (recurrence and survival) in a cohort of 252 patients with oral and oropharyngeal squamous cell cancer (OSCC).

METHODS:

Expression levels of Bmi‐1 and p16 in samples from 252 patients with OSCC were evaluated immunohistochemically using the tissue microarray method. Staining intensity was determined by calculating an intensity reactivity score (IRS). Staining intensity and the localization of expression within tumor cells (nuclear or cytoplasmic) were correlated with overall, disease‐specific, and recurrence‐free survival.

RESULTS:

The majority of cancers were localized in the oropharynx (61.1%). In univariate analysis, patients who had OSCC and strong Bmi‐1 expression (IRS >10) had worse outcomes compared with patients who had low and moderate Bmi‐1 expression (P = .008; hazard ratio [HR], 1.82; 95% confidence interval [CI], 1.167‐2.838); this correlation was also observed for atypical cytoplasmic Bmi‐1 expression (P = .001; HR, 2.164; 95% CI, 1.389‐3.371) and for negative p16 expression (P < .001; HR, 0.292; 95% CI, 0.178‐0.477). The combination of both markers, as anticipated, had an even stronger correlation with overall survival (P < .001; HR, 8.485; 95% CI, 4.237‐16.994). Multivariate analysis demonstrated significant results for patients with oropharyngeal cancers, but not for patients with oral cavity tumors: Tumor classification (P = .011; HR, 1.838; 95%CI, 1.146‐2.947) and the combined marker expression patterns (P < .001; HR, 6.254; 95% CI, 2.869‐13.635) were correlated with overall survival, disease‐specific survival (tumor classification: P = .002; HR, 2.807; 95% CI, 1.477‐5.334; combined markers: P = .002; HR, 5.386; 95% CI, 1.850‐15.679), and the combined markers also were correlated with recurrence‐free survival (P = .001; HR, 8.943; 95% CI, 2.562‐31.220).

CONCLUSIONS:

Cytoplasmic Bmi‐1 expression, an absence of p16 expression, and especially the combination of those 2 predictive markers were correlated negatively with disease‐specific and recurrence‐free survival in patients with oropharyngeal cancer. Therefore, the current results indicate that these may be applicable as predictive markers in combination with other factors to select patients for more aggressive treatment and follow‐up. Cancer 2011;. © 2011 American Cancer Society.     

Phase 3 trial of everolimus for metastatic renal cell carcinoma

BACKGROUND:

A phase 3 trial demonstrated superiority at interim analysis for everolimus over placebo in patients with metastatic renal cell carcinoma (mRCC) progressing on vascular endothelial growth factor receptor–tyrosine kinase inhibitors. Final results and analysis of prognostic factors are reported.

METHODS:

Patients with mRCC (N = 416) were randomized (2:1) to everolimus 10 mg/d (n = 277) or placebo (n = 139) plus best supportive care. Progression‐free survival (PFS) and safety were assessed to the end of double‐blind treatment. Mature overall survival (OS) data were analyzed, and prognostic factors for survival were investigated by multivariate analyses. A rank‐preserving structural failure time model estimated the effect on OS, correcting for crossover from placebo to everolimus.

RESULTS:

The median PFS was 4.9 months (everolimus) versus 1.9 months (placebo) (hazard ratio [HR], 0.33; P < .001) by independent central review and 5.5 months (everolimus) versus 1.9 months (placebo) (HR, 0.32; P < .001) by investigators. Serious adverse events with everolimus, independent of causality, in ≥5% of patients included infections (all types, 10%), dyspnea (7%), and fatigue (5%). The median OS was 14.8 months (everolimus) versus 14.4 months (placebo) (HR, 0.87; P = .162), with 80% of patients in the placebo arm crossed over to everolimus. By the rank‐preserving structural failure time model, the survival corrected for crossover was 1.9‐fold longer (95% confidence interval, 0.5‐8.5) with everolimus compared with placebo only. Independent prognostic factors for shorter OS in the study included low performance status, high corrected calcium, low hemoglobin, and prior sunitinib (P < .01).

CONCLUSIONS:

These results established the efficacy and safety of everolimus in patients with mRCC after progression on sunitinib and/or sorafenib. Cancer 2010. © 2010 American Cancer Society.     

Impact of Clinicopathologic Features on the Efficacy of PD-1/PD-L1 Inhibitors in Patients With Previously Treated Non–small-cell Lung Cancer

Background

The current study aimed to comprehensively investigate the impact of various clinicopathologic features on the efficacy of programmed cell death-1 (PD-1) and ligand (PD-L1) inhibitors in patients with previously treated non–small-cell lung cancer (NSCLC).