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.     

Role of hepatic resection in patients with intermediate‐stage hepatocellular carcinoma: A multicenter study from Japan

Transarterial chemoembolization (TACE) is recommended for patients with intermediate‐stage (Barcelona Clinic Liver Cancer criteria B [BCLC‐B]) hepatocellular carcinoma (HCC). However, patients with BCLC‐B HCC can differ in background factors related to hepatic function, as well as tumor size and number. In the present study, we clarified the role of hepatic resection in patients with BCLC‐B HCC. A total of 489 BCLC‐B HCC patients with Child–Pugh class A disease initially treated with hepatic resection or TACE were included. After propensity score matching (n = 264), hepatic resection (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.35–0.91) was independently associated with survival in the multivariate analysis. We then divided patients into two groups based on the results of statistical analysis. There were 170 patients treated with resection and 319 with TACE. Child–Pugh score and number of tumors (cut‐off, three tumors) were independently associated with type of HCC treatment in the multivariate analysis. We then divided patients in Group A (Child–Pugh score of 5 and ≤3 tumors; n = 186) and Group B (Child–Pugh score of 6 or ≥4 tumors; n = 303). In Group A, cumulative survival was significantly higher in the hepatic resection group than in the TACE group (P = 0.014). In Cox proportional hazards models, hepatic resection (HR, 0.38; 95% CI, 0.23–0.64) was independently associated with survival in Group A patients. In Group B, treatment status was not associated with overall survival. Hepatic resection should be considered in patients with a Child–Pugh score of 5 and ≤3 tumors, despite having BCLC‐B HCC.     

Intra‐arterial iodine‐131‐lipiodol for unresectable hepatocellular carcinoma

BACKGROUND:

Hepatic artery administration of iodine‐131‐Lipiodol serves as a modality that delivers targeted radiation therapy to hepatocellular carcinoma. Its efficacy has been promising according to trials conducted in the adjuvant setting after hepatic resection. Further investigation of its role in the palliative setting is warranted.

METHODS:

A retrospective review of 72 patients with unresectable hepatocellular carcinoma treated with iodine‐131‐Lipiodol and followed up by the St. George Hospital Sydney's hepatobiliary service was conducted. Efficacy of treatment was determined based on progression‐free and overall survival as the endpoints using the Kaplan‐Meier method.

RESULTS:

Sixty men and 12 women with a mean age of 65 years (standard deviation = 11) underwent iodine‐131‐Lipiodol treatment. Chronic viral hepatitis was present in 29 (41%) patients. Fifty (69%) patients were Child‐Pugh class A. Median progression‐free survival was 6 months, and overall survival was 14 months; the 1‐, 2‐, and 3‐year survival rates were 52%, 33% and 20%, respectively. Factors associated with survival include the American Joint Committee on Cancer stage (P = .03), Barcelona Clinic Liver Cancer stage (P = .05), Cancer of the Liver Italian Program score (P = .008), tumor size (P = .01), extrahepatic disease (P < .001), previous surgery (P = .02), and response to treatment (P < .001). The response to treatment was identified through a multivariate analysis as the single independent predictor for survival (hazard ratio, 3.5; 95% confidence interval, 2.2‐5.4; P < .001).

CONCLUSIONS:

Encouraging survival outcomes may be derived through administration of iodine‐131‐Lipiodol in patients with unresectable hepatocellular carcinoma. The overall success of treatment may be determined by the response to treatment. Cancer 2010. © 2010 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.     

Interval to biochemical failure as a biomarker for cause-specific and overall survival after dose-escalated external beam radiation therapy for prostate cancer

BACKGROUND:

After external beam radiation therapy (EBRT) for prostate cancer, a short interval to biochemical failure of <18 months has been proposed as a surrogate for cause‐specific survival. Because EBRT dose influences biochemical failure, the authors investigated the interval to biochemical failure in a cohort of patients treated with dose‐escalated EBRT.

METHODS:

From 1998 to 2008, 710 patients were treated with EBRT (≥75 grays) ± androgen deprivation therapy (ADT) at the University of Michigan. Biochemical failure was defined using the Phoenix consensus definition (nadir + 2 ng/mL). A short interval to biochemical failure was defined as <18 months after completing radiotherapy and/or ADT. The associations between biochemical failure, the interval to biochemical failure, and clinical factors with cause‐specific survival (CSS) and overall survival (OS) were evaluated.

RESULTS:

There were 149 biochemical failures (21%), and short interval to biochemical failure accounted for 14% and 40% of biochemical failures in those with intermediate‐risk or high‐risk disease, respectively. Biochemical failure impacted CSS (P < .0001) but not OS (P = .36). However, a short interval to biochemical failure predicted decreased CSS (P < .0001; hazard ratio [HR], 5.6; 95% confidence interval [CI], 2.4‐13.0) and OS (P < .0001; HR, 4.8; 95% CI, 2.3‐10.3) when compared with a long interval to biochemical failure. The 8‐year OS was 78% without biochemical failure, compared with 87% with a long interval to biochemical failure (P = .1; HR, 0.7; 95% CI, 0.4‐1.1) and 38% with a short interval to biochemical failure (P < .0001; HR, 3.7; 95% CI, 2.3‐5.9). On multivariate analysis, a short interval to biochemical failure increased the risk of prostate cancer death (P < .0001; HR, 18.1; 95% CI, 8.4‐39) and all cause mortality (P = .0027; HR, 1.5; 95% CI, 1.2‐2.1), whereas a long interval to biochemical failure did not.

CONCLUSIONS:

The relation between the interval to biochemical failure, CSS, and OS was independently validated in patients treated with dose‐escalated EBRT. Further evaluation of the interval to biochemical failure as a surrogate endpoint is warranted. Cancer 2012. © 2011 American Cancer Society.     

Phase 2 trial of linifanib (ABT‐869) in patients with unresectable or metastatic hepatocellular carcinoma

BACKGROUND:

The efficacy and safety of linifanib (ABT‐869), a selective inhibitor of vascular endothelial growth factor and platelet‐derived growth factor receptor tyrosine kinases, were assessed in this phase 2, single‐arm, open‐label, multicenter trial.

METHODS:

Eligible patients had unresectable or metastatic hepatocellular carcinoma and had received ≤ 1 prior systemic therapy. Patients received oral linifanib at a fasting dose of 0.25 mg/kg,. The primary endpoint was the progression‐free rate at 16 weeks. Tumor response was assessed every 8 weeks. Secondary endpoints included the time to disease progression, overall survival, and objective response rate. Safety was also assessed.

RESULTS:

Of the 44 patients enrolled, the majority were Asian (89%), had received no prior systemic therapy (82%), had Child‐Pugh class A hepatic function (86%), and had hepatitis B virus infection (61%). The estimated progression‐free rate at 16 weeks was 31.8% (34.2% for patients with Child‐Pugh class A hepatic function), the estimated objective response rate was 9.1% (10.5% for patients with Child‐Pugh class A hepatic function), the median time to disease progression was 3.7 months (3.7 months for patients with Child‐Pugh class A hepatic function), and the median overall survival was 9.7 months (10.4 months for patients with Child‐Pugh class A hepatic function). The most common linifanib‐related adverse events were diarrhea (55%) and fatigue (52%). The most common linifanib‐related grade 3/4 adverse events were hypertension (25%) and fatigue (14%). Serum levels of biomarkers cancer antigen (CA) 125, cytokeratin fragment (CYFRA)21.1, and protein induced by vitamin K absence or antagonist II (PIVKA) demonstrated potential as prognostic indicators of patient response or outcome.

CONCLUSIONS:

Single‐agent linifanib was found to be clinically active in patients with advanced hepatocellular carcinoma, with an acceptable safety profile. Cancer 2013. © 2012 American Cancer Society.     

Phase 2 open‐label study of single‐agent sorafenib in treating advanced hepatocellular carcinoma in a hepatitis B–endemic Asian population

BACKGROUND:

The current study was a phase 2 open–label study to evaluate the efficacy and tolerability of single‐agent sorafenib in the treatment of advanced HCC patients in a hepatitis B–endemic Asian population.

METHODS:

Patients with advanced hepatocellular carcinoma (HCC) received sorafenib at a dose of 400 mg twice daily in 4‐week cycles. Tumor response was assessed every 3 cycles using Response Evaluation Criteria in Solid Tumors criteria.

RESULTS:

Fifty‐one patients were enrolled in the study and were treated with sorafenib for at least 12 weeks. The median age was 56 years (range, 28‐79 years). Approximately 90% had hepatitis B virus–related HCC. Thirty‐six (71%) patients had underlying Child‐Pugh A cirrhosis, 13 (26%) Child‐Pugh B, and 2 (3%) Child‐Pugh C. Four (8%) patients achieved partial responses, and 9 (18%) patients had stable disease for at least 12 weeks. The median overall survival was 5 months (range, 4‐17 months). Patients without extrahepatic spread, particularly without lung metastasis (P<.01), are more likely to benefit from sorafenib treatment. The most common toxicities were diarrhea (67%), malaise (55%), and hand‐foot‐skin reaction (54%). The majority of patients had transient liver function derangement. Patients with and without underlying portal vein thrombosis had similar therapeutic benefits and likewise shared a similar treatment‐related toxicity profile with sorafenib treatment.

CONCLUSIONS:

Single‐agent sorafenib demonstrates good efficacy and acceptable tolerability in treating an advanced HCC patient population in a hepatitis B–endemic area. The presence of lung metastasis predicts poor response to sorafenib in advanced HCC patients. Cancer 2009. © 2009 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.     

Stage IV breast cancer in the era of targeted therapy

BACKGROUND:

Multiple studies have suggested that resection of the primary tumor improves survival in patients with stage IV breast cancer, yet in the era of targeted therapy, the relation between surgery and tumor molecular subtype is unknown. The objective of the current study was to identify subsets of patients who may benefit from primary tumor treatment and assess the frequency of local disease progression.

METHODS:

Patients presenting with stage IV breast cancer and intact primary tumors (n = 186) were identified from a prospectively maintained clinical database (2000‐2004) and clinical data were abstracted (grading determined according to the American Joint Committee on Cancer staging system).

RESULTS:

Surgery was performed in 69 (37%) patients: 34 (49%) patients with unknown metastatic disease at the time of surgery, 15 (22%) patients for local control, 14 (20%) patients for palliation, and in 6 (9%) patients to obtain tissue. Surgical patients were more likely to be HER‐2/neu negative (P = .001), and to have smaller tumors (P = .05) and solitary metastasis (P <.001). Local therapy included axillary lymph node clearance in 33 (48%) patients and postoperative radiotherapy in 9 (13%) patients. The median survival was 35 months. Cox regression analysis identified estrogen receptor (ER) positivity (hazard ratio [HR], 0.47; 95% confidence interval [95% CI], 0.29‐0.76), progesterone receptor (PR) positivity (HR, 0.57; 95% CI, 0.36‐0.90), and HER‐2/neu amplification (HR, 0.51; 95% CI, 0.34‐0.77) as being predictive of improved survival. There was a trend toward improved survival with surgery (HR, 0.71; 95% CI, 0.47‐1.06). On exploratory analyses, surgery was found to be associated with improved survival in patients with ER/PR positive or HER‐2/neu?amplified disease (P = .004). No survival benefit was observed in patients with triple‐negative disease.

CONCLUSIONS:

Although a trend toward improved survival with surgery was observed, it was noted most strongly in patients with ER/PR positive and/or HER‐2/neu?amplified disease. This suggests that the impact of local control is greatest in the presence of effective targeted therapy, and supports the need for further study to define patient subsets that will benefit most. Cancer 2010. © 2010 American Cancer Society.     

Improved survival in patients with early stage low‐grade follicular lymphoma treated with radiation

BACKGROUND:

External beam radiation therapy (RT) is the standard treatment for stage I‐II, grade 1‐2 follicular lymphoma. Because of an indolent natural history, some advocate alternative management strategies, including watchful waiting for this disease. The relative improvement in outcomes for patients treated with and without RT has never been tested in randomized trials.

METHODS:

The Surveillance, Epidemiology, and End Results database was queried for adult patients with stage I‐II, grade 1‐2 follicular lymphoma diagnosed from 1973 to 2004. Retrievable patient data included age, sex, race, stage, extranodal disease, and treatment with RT within the first year after diagnosis. Actuarial overall survival (OS) and disease‐specific survival (DSS) were analyzed.

RESULTS:

A total of 6568 patients were identified. DSS at 5, 10, 15, and 20 years in the RT group was 90%, 79%, 68%, and 63% versus 81%, 66%, 57%, and 51% in the no RT group (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.55‐0.68; P < .0001). OS at 5, 10, 15, and 20 years in the RT group was 81%, 62%, 45%, and 35% versus 71%, 48%, 34%, and 23% in patients not receiving RT (HR, 0.68; 95% CI, 0.63‐0.73; P < .0001). On multivariate analysis, upfront RT remained independently associated with improved DSS (P < .0001, Cox HR, 0.65; 95% CI, 0.57‐0.72) and OS (P < .0001; Cox HR, 0.73; 95% CI, 0.67‐0.79). Lymphoma was the most common cause of death (52%). Only 34% of patients received upfront RT.

CONCLUSIONS:

Upfront RT was associated with improved DSS and OS compared with alternate management approaches, a benefit that persisted over time. This benefit suggests that watchful waiting with administration of salvage therapies on progression/relapse do not compensate for inadequate initial definitive treatment. Although it is the standard of care for this disease, RT for early stage low‐grade follicular lymphoma is greatly underused in the US population; increased use of upfront RT could prevent thousands of deaths from lymphoma in these patients. Cancer 2010. © 2010 American Cancer Society.     

Race,ethnicity, and socioeconomic status influence the survival of patients with hepatocellular carcinoma in the United States

BACKGROUND:

Racial, ethnic, and socioeconomic disparities in the survival of patients with hepatocellular carcinoma (HCC) continue to exist. The authors of this report hypothesized that these differences result from inequities in access to care and in response to therapy.

METHODS:

Patients with HCC (n = 20,920) were identified from the Surveillance, Epidemiology, and End Results (SEER) database, and patients who underwent liver transplantation for HCC (n = 4735) were identified from the United Network for Organ Sharing (UNOS) database. Clinical and pathologic factors were compared after patients were stratified by race and ethnicity.

RESULTS:

The survival of patients with HCC improved over time for all racial, ethnic, and income groups (P < .001). Black and low income individuals had the poorest long‐term survival (P < .001). On multivariate analysis, black race was predictive of the poorest survival (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.09‐1.22; P < .001), whereas Asian race was associated with the best survival (HR, 0.87; 95% CI, 0.83‐0.91; P < .001). After liver transplantation, black patients had the worst graft survival and overall survival (median survival [MS], 30.5 months and 39.7 months, respectively; P < .001), whereas Hispanics had the best survival (MS, 83.4 months and 86.6 months, respectively; P < .001). In a multivariate analysis of transplantation patients, race and ethnicity were associated significantly with outcome.

CONCLUSIONS:

Significant racial and ethnic disparities in the outcome of patients with HCC persist despite the receipt of comparable treatment. The authors concluded that further investigations are warranted to identify the reasons for the stark disparity in outcomes between black patients and Hispanic patients after liver transplantation for HCC. Cancer 2010. © 2010 American Cancer Society.     

The use of single‐agent sorafenib in the treatment of advanced hepatocellular carcinoma patients with underlying Child‐Pugh B liver cirrhosis

BACKGROUND:

This study explored the efficacy, tolerability, and survival benefits of using sorafenib in patients with Child‐Pugh class B (CPB) cirrhosis.

METHODS:

Patients with advanced hepatocellular carcinoma who were treated with sorafenib at Queen Mary Hospital, Hong Kong, China, were analyzed retrospectively. Treatment outcomes were analyzed according to their respective Child‐Pugh status. Patients with CPB disease were further divided into CPB7 (those with a score of 7) and CPB8‐9 (a score of 8 or 9) subgroups.

RESULTS:

The baseline demographic parameters were comparable between 108 patients with Child‐Pugh class A (CPA) disease and 64 CPB patients. Both clinical benefit rate (21.3% vs 32.4% vs 14.8%; P = .23) and progression‐free survival (median: 3.2 months vs 3.2 months vs 2.3 months; P = .26) were similar among CPA, CPB7, and CPB8‐9 groups, respectively. The overall survival was different among these groups (P = .002) and showed a trend toward worse outcome in CPB patients: the median was 6.1, 5.4, and 2.7 months among CPA, CPB7, and CPB8‐9 patients, respectively. The commonest grade 3/4 adverse events were hand‐foot syndrome (13.5%), diarrhea (9.9%), and rash (7.0%). Grade 3/4 leukopenia, thrombocytopenia, and anemia occurred in 2.9%, 5.3%, and 8.8% of the patients, respectively. Overall, the 3 groups of patients experienced similar incidence of most of these adverse events. Nonetheless, CPB patients experienced more anemia (P = .01), gastrointestinal bleeding (P = .02), and hepatic encephalopathy (P = .02).

CONCLUSIONS:

CPA and CPB patients tolerated sorafenib similarly and derived similar clinical and progression‐free survival benefit. Among CPB patients, most benefits were observed in patients with a score of 7. Nevertheless, CPB patients were more susceptible to developing cirrhotic complications, and thus more vigilant surveillance is needed. Cancer 2012. © 2012 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.     

Predictors of competing mortality in early breast cancer

BACKGROUND:

Death in the absence of disease recurrence (competing mortality) is an important determinant of disease‐free survival (DFS) in early breast cancer. The authors sought to identify predictors of this event using competing risks modeling.

METHODS:

A cohort study was made of 1231 consecutive women with stage I to II invasive breast cancer diagnosed between 1986 and 2004, treated with breast conservation therapy. Median follow‐up was 82 months. The authors used a parametric competing risks regression model to analyze factors associated with the cumulative incidence of competing mortality. They generated a risk score from the model coefficient estimates and stratified patients according to low and high risk score for analysis.

RESULTS:

Ten‐year DFS was 69.7% (95% confidence interval [CI], 66.2%‐72.9%). The 10‐year cumulative incidence of locoregional recurrence (LRR) was 4.4% (95% CI, 3.0%‐5.8%), distant recurrence was 7.1% (95% CI, 5.4%‐8.9%), and competing mortality was 18.7% (95% CI, 15.9%‐21.6%). On multivariate analysis, competing mortality was associated with increasing age (hazard ratio [HR], 1.83 per 10 years; 95% CI, 1.58‐2.12), black race (HR, 1.71; 95% CI, 1.17‐2.51), and comorbid disease (HR, 1.93, 95% CI, 1.40‐2.65). Ten‐year cumulative incidences of competing mortality, locoregional recurrence, and distant recurrence for patients at low (n = 638) versus high (n = 593) risk of competing mortality were 7.2% versus 30.6% (P < .001), 4.4% versus 4.4% (P = .97), and 8.6% versus 5.6% (P = .12), respectively.

CONCLUSIONS:

Competing mortality is an important event influencing 10‐year DFS in early breast cancer and is associated with increasing age, black race, and comorbid disease. Stratifying patients according to competing mortality risk may be useful in designing clinical trials. Cancer 2010. © 2010 American Cancer Society.     

Excellent outcomes with angiographic subsegmentectomy in the treatment of typical hepatocellular carcinoma

BACKGROUND:

The authors successfully adopted an interesting and effective treatment for hepatocellular carcinoma (HCC) referred to as angiographic subsegmentectomy (AS). This treatment involved simultaneous embolization of the peripheral feeding artery and the portal vein. The result was that almost all of the HCC and peripheral liver parenchyma developed complete anatomic necrosis.

METHODS:

To determine the effectiveness of this method, the authors retrospectively studied the local recurrence rates of 49 solitary HCCs and the long‐term survival rates of 120 patients with HCC between 2000 and 2008.

RESULTS:

The results indicated that, in 31 small, solitary HCCs (<2.0 cm), the local recurrence rate was only 9.6%; and, in 10 slightly larger HCCs (<3.0 cm), the local recurrence rate was only 10%. The 5‐year, 8‐year, and 10‐year survival rates for patients with stage I and stage I/Child‐Pugh grade A HCC were 74.27% and 77.65%, 53.05% and 51.76%, and 53% and 51.76%, respectively; and the 5‐year, 8‐year, and 10‐year survival rates for patients with stage II and stage II/Child‐Pugh grade A HCC were 66.21% and 71.41%, 39.9% and 39.60%, and 29.92% and 25%), respectively. There were no severe complications.

CONCLUSIONS:

AS should be investigated further as potential first‐line therapy for the treatment of patients with stage I and II HCC. Cancer 2010. © 2010 American Cancer Society.     

Smoking,alcohol use,obesity, and overall survival from non‐Hodgkin lymphoma

BACKGROUND:

Smoking, alcohol use, and obesity appear to increase the risk of developing non‐Hodgkin lymphoma (NHL), but to the authors' knowledge, few studies to date have assessed their impact on NHL prognosis.

METHODS:

The association between prediagnosis cigarette smoking, alcohol use, and body mass index (BMI) and overall survival was evaluated in 1286 patients enrolled through population‐based registries in the United States from 1998 through 2000. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using Cox regression, adjusting for clinical and demographic factors.

RESULTS:

Through 2007, 442 patients had died (34%), and the median follow‐up for surviving patients was 7.7 years. Compared with never smokers, former (HR, 1.59; 95% CI, 1.12‐2.26) and current (HR, 1.50; 95% CI, 0.97‐2.29) smokers had poorer survival, and poorer survival was found to be positively associated with smoking duration, number of cigarettes smoked per day, pack‐years of smoking, and shorter time since quitting (all P <0.01). Alcohol use was associated with poorer survival (P = 0.03); compared with nonusers. Those drinking >43.1 g/week (median intake among drinkers) had poorer survival (HR, 1.55; 95% CI, 1.06‐2.27), whereas those drinkers consuming less than this amount demonstrated no survival disadvantage (HR, 1.13; 95% CI, 0.75‐1.71). Greater BMI was associated with poorer survival (P = 0.046), but the survival disadvantage was only noted among obese individuals (HR, 1.32 for BMI ≥30 vs BMI 20‐24.9; 95% CI, 1.02‐1.70). These results held for lymphoma‐specific survival and were broadly similar for diffuse large B‐cell lymphoma and follicular lymphoma.

CONCLUSIONS:

NHL patients who smoked, consumed alcohol, or were obese before diagnosis were found to have a poorer overall and lymphoma‐specific survival. Cancer 2010. © 2010 American Cancer Society.     

Body mass index at diagnosis and survival among colon cancer patients enrolled in clinical trials of adjuvant chemotherapy

BACKGROUND:

Although obesity is an established risk factor for developing colon cancer, its prognostic impact and relation to patient sex in colon cancer survivors remains unclear.

METHODS:

The authors examined the prognostic and predictive impact of the body mass index (BMI) in patients with stage II and III colon carcinoma (N = 25,291) within the Adjuvant Colon Cancer Endpoints (ACCENT) database. BMI was measured at enrollment in randomized trials of 5‐fluorouracil–based adjuvant chemotherapy. Association of BMI with the time to recurrence (TTR), disease‐free survival (DFS), and overall survival (OS) were determined using Cox regression models. Statistical tests were 2‐sided.

RESULTS:

During a median follow‐up of 7.8 years, obese and underweight patients had significantly poorer survival compared with overweight and normal‐weight patients. In a multivariable analysis, the adverse prognostic impact of BMI was observed among men but not among women (P_interaction = .0129). Men with class 2 and 3 obesity (BMI ≥35.0 kg/m²) had a statistically significant reduction in DFS (hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.01‐1.33; P = .0297) compared with normal‐weight patients. Underweight patients had a significantly shorter TTR and reduced DFS (HR, 1.18; 95% CI, 1.09‐1.28; P < .0001) that was more significant among men (HR, 1.31; 95% CI, 1.15‐1.50; P < .0001) than among women (HR, 1.11; 95% CI, 1.01‐1.23; P = .0362; P_interaction = .0340). BMI was not predictive of a benefit from adjuvant treatment.

CONCLUSIONS:

Obesity and underweight status were associated independently with inferior outcomes in patients with colon cancer who received treatment in adjuvant chemotherapy trials. Cancer 2013. © 2013 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.     

Impact of low estrogen/progesterone receptor expression on survival outcomes in breast cancers previously classified as triple negative breast cancers

PURPOSE:

To evaluate the impact of low estrogen/progesterone receptor (ER/PR) expression and effect of endocrine therapy on survival outcomes in human epidermal growth factor receptor 2 (HER2)‐negative tumors with ER/PR <10%, previously labeled as triple negative.

METHODS:

In a retrospective review, 1257 patients were categorized according their ER/PR percentages into 3 groups, ER/PR <1% (group A), ER/PR 1% to 5% (group B), and ER/PR 6% to 10% (group C). Kaplan‐Meier product limit method was used to estimate survival outcomes. Cox proportional hazards models was used to adjust for patient and tumor characteristics.

RESULTS

Groups A, B, and C had 897 (71.4%), 241 (19.2%), and 119 (9.4%) patients, respectively. After a median follow‐up of 40 months there was no significant difference in 3‐year recurrence‐free survival (RFS): 64%, 67%, and 77% (P = .34) or overall survival (OS): 79%, 81%, and 88% (P = .33) for groups A, B, and C, respectively. ER/PR expression was not an independent predictor for RFS (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.86‐1.39; P = .46 for group B, and HR, 0.96; 95% CI, 0.66‐1.38; P = .81 for group C, compared with group A), or OS (HR, 1.11; 95% CI, 0.84‐1.46; P = .46 for group B, and HR, 0.94; 95% CI, 0.63‐1.42; P = .78 for group C, compared with group A). Endocrine therapy had no impact on survival outcomes (RFS: P = .10; OS: P = .45) among groups.

CONCLUSIONS:

In this cohort, a low ER/PR level (1%‐5%) does not appear to have any significant impact on survival outcomes. There was a tendency for survival advantages in the ER/PR 6% to 10% is seen. Benefit of endocrine therapy in these patients is unclear. Cancer 2011;. © 2011 American Cancer Society.