Number of metastases, serum lactate dehydrogenase level, and type of treatment are prognostic factors in patients with brain metastases of malignant melanoma

BACKGROUND:

This multicenter study aimed to identify prognostic factors in patients with brain metastases from malignant melanoma (BM‐MM).

METHODS:

In a retrospective survey in 9 cancer centers of the German Cancer Society, 692 patients were identified with BM‐MM during the period 1986 through 2007. Overall survival was analyzed using a Kaplan‐Meier estimator and compared with log‐rank analysis. Cox proportional hazards models were used to identify prognostic factors significant for survival.

RESULTS:

The median overall survival of the entire cohort was 5.0 months (95% confidence interval [95% CI], 4 months‐5 months). Significant prognostic factors in the univariate Kaplan‐Meier analysis were Karnofsky performance status (≥70% vs <70%; P < .001), number of BM‐MM (single vs multiple; P < .001), pretreatment levels of lactate dehydrogenase (LDH) (normal vs elevated; P < .001) and S‐100 (normal vs elevated; P < .001), prognostic groups according to Radiation Therapy Oncology Group (class I vs class II vs class III; P = .0485), and treatment choice (for the cohort with single BM‐MM only) (stereotactic radiotherapy or neurosurgical metastasectomy vs others; P = .036). Cox proportional hazards models revealed pretreatment elevated level of serum LDH (hazard ratio [HR], 1.6; 95% CI, 1.3‐2.0 [P = .00013]) and number of BM‐MM (HR, 1.6; 95% CI, 1.3‐2.0 [P = .00011]) to be independent prognostic variables in the entire cohort, whereas in patients with a single BM‐MM, treatment choice (HR, 1.5; 95% CI, 1.1‐1.9 [P = .0061]) was identified as a unique prognostic factor.

CONCLUSIONS:

The overall survival of patients with BM‐MM primarily depends on the number of metastases and pretreatment level of LDH. In the case of a single brain metastasis, stereotactic radiotherapy or neurosurgical metastasectomy is by far the most important factor for improving survival. Cancer 2011. © 2010 American Cancer Society.     

Prognostic impact of magnetic resonance imaging‐detected cranial nerve involvement in nasopharyngeal carcinoma

BACKGROUND:

The purpose of this study was to evaluate the prognostic value of magnetic resonance imaging (MRI)‐detected cranial nerve (CN) involvement in nasopharyngeal carcinoma (NPC).

METHODS:

Retrospective analysis was made of the magnetic resonance images and medical records of 924 consecutive patients with newly diagnosed NPC.

RESULTS:

Of 924 patients, 82 (8.9%) initially presented with CN palsy. CN involvement was seen on MRI in 333 (36%) patients. In T3‐4 disease, MRI‐evidenced CN involvement was associated with poor 3‐year overall survival (OS) (35.7% vs 89.2%, P = .001) and distant metastasis‐free survival (DMFS) (77.1% vs 87.8%, P = .002) rates. The survival curves of OS and DMFS for T3 disease with MRI‐detected CN involvement approximated those of T4 disease (P = .322 and P = .809, respectively). In patients with MRI‐detected CN involvement, no significant differences were observed in 3‐year OS (78.3% vs 72.9%, P = .120), local relapse‐free survival (LRFS) (89.7% vs 84.1%, P = .154), or DMFS (79.6% vs 74.8%, P = .466) rates between those with and without intracranial or orbital CN involvement. Furthermore, in patients with clinical and/or MRI‐detected CN involvement, there were no significant differences in the 3‐year OS (74.2% vs 80.1%, P = .067), LRFS (86.7% vs 87.9%, P = .899), or DMFS (74.6% vs 84.6%, P = .094) rates between symptomatic and asymptomatic patients.

CONCLUSIONS:

The incidence of MRI‐detected CN involvement was higher than CN palsy. MRI‐detected CN involvement has a negative impact on the prognosis independent of lesion localization and symptoms. Cancer 2009. © 2009 American Cancer Society.     

Significance of bone marrow reticulin fibrosis in chronic lymphocytic leukemia at diagnosis

BACKGROUND:

Bone marrow (BM) biopsies from patients with chronic lymphocytic leukemia (CLL) may show reticulin fibrosis at diagnosis, but its significance remains unclear. This study sought to assess the prognostic impact of BM reticulin fibrosis in patients with previously untreated CLL.

METHODS:

Data was reviewed from untreated CLL patients in the national Israel CLL database, followed during 1987 to 2012. All bone marrow biopsies were graded for reticulin fibrosis using a modified scoring system containing 4 grades (0‐3), based on the European consensus report. Grade of reticulin fibrosis was correlated with overall survival (OS), outcome, and a number of well‐recognized prognostic factors for CLL.

RESULTS:

The final cohort included 176 patients (122 males and 51 females). Median age was 63 years (range, 32‐86 years) and the 5‐year OS was 77.1%. Grade of BM reticulin fibrosis correlated with OS (P < .0001) and mortality (P = .001), and separated patients into 2 groups with different survival curves. Advanced reticulin fibrosis (grades 2‐3) was associated with thrombocytopenia (platelet counts of < 100,000/mm³) (P = .025), anemia (P = .018), elevated β2‐microglobulin < 4000 μg/mL (P = .048), and the presence of 11q deletion (P = .0015).

CONCLUSIONS:

There was a significant correlation between poor survival and grade of BM reticulin fibrosis. This staining procedure is easy to perform and can readily be added routinely when examining BM biopsies in CLL, because the findings do have prognostic implications. Cancer 2013. © 2013 American Cancer Society.     

Cytogenetic profile of patients with acute myeloid leukemia and central nervous system disease

BACKGROUND:

Acute myeloid leukemia (AML) infrequently involves the central nervous system (CNS). This study was undertaken in patients with AML to determine whether cytogenetic findings predict CNS involvement.

METHODS:

The medical records of 1354 patients with AML who were treated at The University of Texas MD Anderson Cancer Center between January 2000 and December 2008 were reviewed. Forty patients (3%) had CNS involvement at time of presentation or disease recurrence, of whom 37 had conventional cytogenetics performed on bone marrow aspirate material. Demographics, treatment, and status at last follow‐up were collected.

RESULTS:

Eleven patients (30%) had a diploid karyotype, and 14 patients (38%) had complex cytogenetics. Only 5 of the 40 patients had CNS disease at diagnosis, and the remaining patients had CNS disease at relapse. Patients who developed CNS disease were younger (P = .019), had a higher white blood cell (WBC) count at diagnosis (P = .001), had higher lactate dehydrogenase level (LDH) levels (P < .0001), and had higher percentages peripheral blast cells (P = .024) at diagnosis compared with the rest of the population. In addition, patients with CNS disease had higher rates of chromosome 16 inversion (P < .001), chromosome 11 abnormality (P = .005), and trisomy 8 (P = .02) and had a tendency toward complex cytogenetics (P = .2) compared with the control group (patients who had AML with no CNS involvement).

CONCLUSIONS:

Patients with AML and CNS disease often had higher LDH levels and WBC counts at diagnosis, and they often presented with chromosome 16 inversion and chromosome 11 abnormalities. The current study indicated that the overall survival of patients with AML who had CNS involvement is poor. Cancer 2012;. © 2011 American Cancer Society.     

Adjuvant therapy for elderly patients with resected gastric adenocarcinoma: population-based practices and treatment effectiveness

BACKGROUND:

A study was undertaken to determine the survival benefit of postoperative chemoradiation therapy for elderly patients with resected gastric adenocarcinoma.

METHODS:

The authors identified 1023 individuals aged 65 years and older (median = 76) who underwent gastrectomy for nonmetastatic stage IB‐IV gastric adenocarcinoma diagnosed between 2000 and 2002 in the linked Surveillance, Epidemiology, and End Results‐Medicare database. They examined factors associated with receiving postoperative chemoradiation and analyzed the survival benefit associated with receiving postoperative chemoradiation.

RESULTS:

Thirty percent of patients received adjuvant chemoradiation. On multivariate analysis, younger age (P < .0001), lymph node involvement (P < .0001), and more recent diagnosis (P = .0284) were associated with receiving chemoradiation. There was a trend toward increased use among patients with less comorbidity (P = .0515). The median follow‐up was 25.5 months, and 62% died. On multivariate survival analysis, older patients (P < .0001) and those with lymph node involvement (P < .0001), T3 or T4 disease (P = .0472), higher grade disease (P = .0355), and more comorbidity (P = .0411) were more likely to die. After adjustment for other factors, receipt of adjuvant chemoradiation therapy did not significantly increase survival (hazard ratio, 0.90; 95% confidence interval, 0.72‐1.12; P = .3453) and did not increase survival in a multivariate analysis that included propensity scores (P = .2090).

CONCLUSIONS:

The authors did not detect a survival benefit, suggesting that some elderly patients with resected gastric adenocarcinoma may not gain a survival benefit from the administration of adjuvant chemoradiation. The analysis had limitations, and the results are hypothesis generating. Future gastric cancer trials should enroll more elderly patients and stratify patients by age to better understand the impact of treatment regimens on older patients. Cancer 2012;. © 2011 American Cancer Society.     

Peripheral blood monitoring of chronic myeloid leukemia during treatment with imatinib, second-line agents, and beyond

BACKGROUND:

The current study was conducted to compare simultaneously obtained bone marrow (BM) cytogenetics (CTG), peripheral blood (PB) and BM fluorescence in situ hybridization (FISH), and quantitative real‐time polymerase chain reaction (Q‐PCR) for BCR‐ABL1 in monitoring response to treatment with tyrosine kinase inhibitors and homoharringtonine (HHT) in patients with chronic myeloid leukemia (CML).

METHODS:

PB and BM FISH (n = 112 samples) and/or Q‐PCR (n = 132 samples) for BCR‐ABL1 were simultaneously obtained in 70 patients with Philadelphia chromosome‐positive (Ph+) CML in chronic (68%), accelerated (16%), and blast phase (16%) before the initiation of therapy and during the course of treatment with imatinib (IM) (n = 40 patients), dasatinib (n = 20 patients), nilotinib (n = 4 patients), bosutinib (n = 18 patients), or HHT (n = 4 patients) for patients with newly diagnosed (n = 13 patients), IM‐sensitive (n = 34 patients), IM‐resistant (n = 30 patients), or IM‐intolerant (n = 9 patients) disease. Eighteen patients were found to have Ph+ variants or karyotypic abnormalities in addition to the Ph+.

RESULTS:

Excellent correlations (r) were observed between PB and BM FISH (r = 0.95) and PB and BM Q‐PCR (r = 0.87), as well as BM CTG and PB FISH (r = 0.89) and PB Q‐PCR (r = 0.82). This correlation was not affected by the presence of the Ph+ variant or additional chromosomal abnormalities, the presence of ABL1 kinase domain mutations, phase of the disease, or treatment.

CONCLUSIONS:

PB FISH and Q‐PCR appear to be reliable methods with which to monitor response to modern therapy in patients with all phases of CML. Cancer 2011. © 2010 American Cancer Society.     

Prognostic impact of extranodal involvement in diffuse large B-cell lymphoma in the rituximab era

BACKGROUND:

Extranodal involvement is considered a poor prognostic factor for patients with diffuse large B‐cell lymphoma (DLBCL); however, the prognostic impact of specific sites of involvement has not been fully elucidated.

METHODS:

The authors retrospectively analyzed 1221 patients treated uniformly with standard R‐CHOP therapy between 2003 and 2006. Patients with distinct forms of DLBCL such as intravascular lymphoma, primary effusion lymphoma, pyothorax‐associated lymphoma, primary central nervous system lymphoma, and intraocular lymphoma were also excluded. The authors evaluated 26 extranodal sites of involvement with respect to prognostic impact. The median age was 64 years (range, 15‐91 years).

RESULTS:

Univariate analysis revealed that patients with involvement of specific extranodal sites had significantly worse overall survival (OS) than did patients without such involvement; these sites included nasal cavity, paranasal sinus, lung, pleura, small intestine, peritoneum, liver, pancreas, stomach, spleen, adrenal gland, testis, bone, bone marrow, peripheral blood, skin, and subcutaneous tissue. Patients with Waldeyer ring involvement had significantly better OS. Multivariate analysis revealed that patients with the involvement of the pleura (P < .001), small intestine (P = .015), peritoneum (P = .002), adrenal gland (P < .001), testis (P = .005), bone marrow (P < .001), and peripheral blood (P = .002) had significantly worse OS, whereas those with Waldeyer ring involvement had significantly better OS (P = .038). Subgroup analysis with the nodal and/or Waldeyer patient group also showed prognostic impact of Waldeyer ring by multivariate analysis (relative risk, 0.3; P = .04).

CONCLUSIONS:

Extranodal involvement affects the prognosis of patients undergoing R‐CHOP therapy for DLBCL. Cancer 2012. © 2011 American Cancer Society.     

Incidence of brain metastases as a first site of recurrence among women with triple receptor-negative breast cancer

BACKGROUND:

This retrospective study sought to define the incidence of brain metastases as a first site of recurrence among women with triple receptor–negative breast cancer (TNBC).

METHODS:

A total of 2448 patients with stage I through III TNBC who were diagnosed between 1990 and 2010 were identified. We computed the cumulative incidence of developing brain metastases as a first site of recurrence at 2 and 5 years. Cox proportional hazards models were fitted to determine factors that could predict for the development of brain metastases as a first site of recurrence. The Kaplan‐Meier product limit method was used to compute survival following a diagnosis of brain metastases.

RESULTS:

At a median follow‐up of 39 months, 115 (4.7%) patients had developed brain metastases as a first site of recurrence. The cumulative incidence at 2 and 5 years was 3.7% (95% confidence interval [CI] = 2.9%‐4.5%) and 5.4% (95% CI = 4.4%‐6.5%), respectively. Among patients with stage I, II, and III disease, the 2‐year cumulative incidence of brain metastases was 0.8%, 3.1%, and 8%, respectively (P < .0001). The 5‐year cumulative incidence was 2.8%, 4.6%, and 9.6% among patients with stage I, II, and III disease, respectively (P < .0001). In the multivariable model, patients with stage III disease had a significant increase in the risk of developing brain metastases as a first site of recurrence (hazards ratio = 3.51; 95% CI = 1.85‐6.67; P = .0001) compared to patients with stage I disease. Those with stage II disease had a nonsignificant increased risk of developing brain metastases as a first site of recurrence (hazards ratio = 1.61; 95% CI = 0.92‐2.81; P = .10) compared with patients with stage I disease. Median survival following a diagnosis of brain metastases was 7.2 months (range, 5.7‐9.4 months).

CONCLUSIONS:

Patients with nonmetastatic TNBC have a high early incidence of developing brain metastases as a first site of recurrence, which is associated with subsequent poor survival. Patients with stage III TNBC in particular would be an ideal cohort in which to research preventive strategies. Cancer 2012. © 2012 American Cancer Society.     

Prognostic factors associated with progression of smoldering multiple myeloma to symptomatic form

BACKGROUND:

Smoldering multiple myeloma (SMM) presents a high risk of progression to symptomatic MM (sy‐MM). Herein, we analyzed some predictors of development of sy‐MM. In 144 patients with SMM, we also compared the risk of progression predicted by bone marrow plasma cell (BMPC) involvement on the bone marrow biopsy (BMB) versus bone marrow aspirates (BMA).

METHODS:

From January 1980 to July 2010, 397 patients with SMM observed in 12 centers of the Multiple Myeloma GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) Latium Working Group have been analyzed. At progression to sy‐MM, the severity of clinical presentation was graded according to the need of intensive supportive care.

RESULTS:

After a median follow‐up of 135 months, the cumulative incidence of progression rates to sy‐MM were 45%, 55%, and 75% at 10, 15, and 20 years, respectively. Hemoglobin ≤12.5 g/dL, monoclonal component ≥2.5 g/dL, and BMPC ≥60% were the only parameters negatively affecting the cumulative incidence of progression. In particular, 10 of 397 (2.5%) patients with BMPC ≥60% had a 5.6‐fold increased risk of fast progression (within 2 years), which occurred with severe clinical manifestations in 62% of cases. BMB was more sensitive for the detection of BMPC involvement, even though BMA was a more reliable indicator of a rapid progression to sy‐MM.

CONCLUSIONS:

The highest risk of rapid evolution to sy‐MM and the severity of clinical manifestation at the progression suggest that SMM patients with a BMPC ≥60% should be treated soon after diagnosis. Moreover, BMPC is a more reliable index for progression to sy‐MM if assessed by BMA. Cancer 2012. © 2012 American Cancer Society.     

Long‐term follow‐up of haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for the treatment of leukemia

BACKGROUND:

Many patients who require allogeneic hematopoietic stem cell transplantation (allo‐HSCT) lack a human leukocyte antigen (HLA)‐matched donor. Recently, a new strategy was developed for HLA‐mismatched/haploidentical transplantation from family donors without in vitro T cell depletion (TCD).

METHODS:

Over the past 9 years, 756 patients underwent haploidentical transplantation using a protocol developed by the authors, which combines granulocyte‐colony stimulating factor–primed bone marrow (G‐BM) and peripheral blood stem cells without in vitro TCD. The long‐term outcome with this treatment modality was reported, and a risk‐factor analysis was provided.

RESULTS:

Of these patients, 752 (99%) achieved sustained, full donor chimerism. The incidence of grades 2 through 4 acute graft‐versus‐host disease (GVHD) was 43%, and the 2‐year cumulative incidence of total chronic GVHD was 53%. The 3‐year cumulative incidence of nonrelapse mortality was 18%. The 2‐year cumulative incidences of relapse were 15% and 26% in the standard‐risk and high‐risk groups, respectively. Of the 756 patients, 480 survived throughout the follow‐up period of 1154 days (range: 335‐3511 days) with the 3‐year leukemia‐free survival rates of 68% and 49% in the standard‐risk and high‐risk groups, respectively. Lower leukemia‐free survival was associated with high‐risk disease status (P = .001), chronic myelogenous leukemia disease type (P = .004), neutrophil engraftment beyond 13 days after transplant (P = .012), and the occurrence of grades 2 through 4 acute GVHD (P = .019).

CONCLUSIONS:

The results from the authors' 9‐year experience showed that G‐BM combined with peripheral blood stem cells from haploidentical donors, without in vitro TCD, is a reliable source of stem cells for transplantation by using the protocol developed by the authors. Cancer 2013. © 2012 American Cancer Society.     

Predicting survival of patients with hypocellular myelodysplastic syndrome: Development of a disease-specific prognostic score system

BACKGROUND:

Although most patients with myelodysplastic syndrome (MDS) exhibit bone marrow hypercellularity, a subset of them present with a hypocellular bone marrow. Specific factors associated with poor prognosis have not been investigated in patients with hypocellular MDS.

METHODS:

The authors studied a cohort of 253 patients with hypocellular MDS diagnosed at The University of Texas MD Anderson Cancer Center between 1993 and 2007 and a cohort of 1725 patients with hyper‐/normocellular MDS diagnosed during the same time period.

RESULTS:

Patients with hypocellular MDS presented more frequently with thrombocytopenia (P < .019), neutropenia (P < .001), low serum β‐2 microglobulin (P < .001), increased transfusion dependency (P < .001), and intermediate‐2/high‐risk disease (57% vs 42%, P = .02) compared with patients with hyper‐/normocellular MDS. However, no difference in overall survival was observed between the 2 groups (P = .28). Multivariate analysis identified poor performance status (Eastern Cooperative Oncology Group ≥2), low hemoglobin (<10 g/dL), unfavorable cytogenetics (?7/7q or complex), increased bone marrow blasts (≥5%), and high serum lactate dehydrogenase (>600 IU/L) as adverse independent factors for survival.

CONCLUSIONS:

A new prognostic model based on these factors was built that segregated patients into 3 distinct risk categories independent of International Prognostic Scoring System (IPSS) score. This model is independent from the IPSS, further refines IPSS‐based prognostication, and may be used to develop of risk‐adapted therapeutic approaches for patients with hypocellular MDS. Cancer 2012. © 2012 American Cancer Society.     

Prognostic significance of baseline positron emission tomography and importance of clinical complete response in patients with esophageal or gastroesophageal junction cancer treated with definitive chemoradiotherapy

BACKGROUND:

Metabolic imaging is of interest in esophageal cancer; however, the usefulness of initial standardized uptake value (SUV) in positron emission tomography (PET) is unknown in patients with esophageal or gastroesophageal carcinoma treated with definitive chemoradiotherapy. The authors hypothesized that initial SUV would correlate with patient outcome.

METHODS:

The authors retrospectively analyzed esophageal or gastroesophageal carcinoma patients who had baseline PET and endoscopic ultrasonography in addition to other routine staging. All patients received definitive chemoradiotherapy. Multiple statistical methods were used.

RESULTS:

The authors analyzed 209 consecutive esophageal or gastroesophageal carcinoma patients treated with definitive chemoradiation for outcome; of these, 180 had baseline PET for additional analyses. The median overall survival (OS) for all patients was 20.7 months (95% confidence interval, 18.8‐26.3). Patients with clinical complete response (CR) lived longer than those with less than clinical CR (P < .0001). The median initial SUV was 12.7 (range, 0‐51). Higher initial SUV was associated with longer tumors (P = .0001), higher T‐stage status (P < .0001), positive N‐stage status (P = .0001), higher overall stage (P < .0001), lack of clinical CR (P = .0002), and squamous cell histology (P < .0001). In the univariate analysis, initial SUV was associated with OS (Cox model, P = .016; log‐rank test, P = .002). In the multivariate analysis, initial SUV dichotomized by the median value (P = .024) and tumor grade (P = .016) proved to be independent OS prognosticators. Median initial SUV for clinical CR patients was 10.2, compared with 15.3 for less than clinical CR patients (P = .0058).

CONCLUSIONS:

The data indicate that a higher initial SUV is associated with poorer OS in patients with esophageal or gastroesophageal carcinoma receiving definitive chemoradiation. Upon validation, baseline PET may become a useful stratification factor in randomized trials and for individualizing therapy. Cancer 2011;. © 2011 American Cancer Society.     

Solitary plasmacytomas: outcome and prognostic factors after definitive radiation therapy

BACKGROUND:

The objective of this study was to review the outcome of patients with solitary plasmacytoma (SP) after definitive radiation therapy.

METHODS:

The authors retrospectively reviewed 84 patients with SP who were diagnosed and treated at The University of Texas MD Anderson Cancer Center during 1988 to 2008. The impact of tumor anatomic site, tumor size, and the presence of serum and urinary paraprotein at diagnosis was assessed on local control, survival, and the risk of developing multiple myeloma (MM).

RESULTS:

Fifty‐nine patients (70%) had bone SP, and 25 patients (30%) had extramedullary SP. Serum paraprotein was present in 39 patients (46%). The median radiation dose was 45 grays (Gy) (range, 36‐53.4 Gy). Local control was achieved in 77 patients (92%). Neither radiation dose nor tumor size predicted local control. The 5‐year rate of progression to MM was 47% and was higher for patients with bone SP (56% vs 30% for extramedullary SP; P = .021), and patients who had serum paraprotein detected at diagnosis (60% vs 39%; P = .016). On univariate analysis, patients aged <60 years and men had higher rates of progression to MM, although the differences were not significant (P = .048 and P = .29, respectively). Multivariate analysis revealed that bone location and serum protein at diagnosis were associated statistically with progression to MM. The 5‐year overall survival rate for the entire patient cohort was 78%, and no difference was observed between patients who had bone SP versus extramedullary SP (76% vs 85%, respectively; P = .274).

CONCLUSIONS:

The current results indicated that definitive radiation therapy for SP can provide excellent local control. Progression to MM remains the main problem and is more common among patients with bone SP and those who have serum paraprotein detected at diagnosis. Cancer 2011;. © 2011 American Cancer Society.     

Non‐small cell lung cancer brain metastasis screening in the era of positron emission tomography‐CT staging: Current practice and outcomes

Introduction

Several clinical guidelines indicate that brain metastasis screening (BMS) should be guided by disease stage in non‐small cell lung cancer (NSCLC). We estimate that screening is performed more broadly in practice, and patients undergo brain imaging at considerable cost with questionable benefit. Our aim was to quantify the use and detection rate of BMS in a contemporary cohort staged with ¹⁸F‐fluorodeoxyglucose positron emission tomography/computed tomography (PET‐CT).

Methods

We conducted a retrospective review of prospectively collected data from three major lung cancer referral centres in Brisbane between January 2011 and December 2015. Patients included had a new diagnosis of NSCLC and had undergone a PET‐CT to stage extra‐cranial disease. BMS was defined as dedicated brain imaging with contrast‐enhanced computed tomography (CE‐CT) or magnetic resonance (MR), in the absence of clinically apparent neurological deficits.

Results

A total of 1751 eligible cases were identified and of these 718 (41%) underwent BMS. The majority had CE‐CT imaging (n = 703). Asymptomatic brain metastases (BM) were detected in 18 patients (2.5%). Of these patients, 12 had concurrent non‐brain metastases. Only six patients (0.8%) had BM alone. The rate of detection increased with N‐stage (P = 0.02) and overall stage (P < 0.001). It was 0.5%, 1%, 1.6% and 7.3% for stage I, II, III and IV respectively. The overall screening rate increased with T‐stage (P = 0.001), N‐Stage (P < 0.001) and overall stage (P < 0.001).

Conclusions

Non‐small cell lung cancer BMS practices remain at odds with published guidelines. The low number of occult BMs detected supports the existing international recommendations. Rationalising BMS would minimise the burden on patients and the health care system.     

Appearance of monoclonal plasma cell diseases in whole‐body magnetic resonance imaging and correlation with parameters of disease activity

The aim of our study was to assess in which way different infiltration patterns of monoclonal plasma cell diseases in whole‐body (wb) magnetic resonance imaging (MRI) are associated with clinical stages, plasma cell content in bone marrow samples and established serum markers of disease activity. Institutional review board approval was obtained. We performed wb‐MRI in 547 consecutive, unselected and untreated patients with monoclonal gammopathy of undetermined significance (MGUS, n = 138), smoldering myeloma (SMM, n = 157) and multiple myeloma (MM, n = 252) on two 1.5 T MRI‐scanners with body array coils. The studies were evaluated in consensus by two experienced radiologists blinded to the diagnosis. We observed focal lesions in 23.9% (MGUS), 34.4% (SMM) and 81.3% (MM), respectively. A diffuse infiltration pattern was detected in 38.4%, 45.9% and 71%, respectively. The differences between all infiltration patterns were significant (p < 0.0001). The presence of focal lesions and the presence of a diffuse bone marrow infiltration was associated with an increased plasma cell percentage in bone marrow samples (median 22% vs. 14%, 26% vs. 10%, both p < 0.0001) and monoclonal protein concentration (median 18 g/dl vs. 13 g/dl, p = 0.003, 20 g/dl vs. 11 g/dl, p < 0.0001). Further categorization of the diffuse infiltration patterns in wb‐MRI into “salt‐and‐pepper,” moderate and severe identified significant associations with M‐protein (median g/dl for S+P/moderate/severe 23/18/25, p = 0.04), plasma cell percentage in the bone marrow (median 25%/24%/40%, p = 0.02), and age (median years 67/60/57, p < 0.0001). Bone marrow infiltration in wb‐MRI is significantly different between the various stages of plasma cell disease and correlates well with established markers of disease activity.     

Does the revised International Federation of Gynecology and Obstetrics staging system for endometrial cancer lead to increased discrimination in patient outcomes?

BACKGROUND:

Recent changes were made to the International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer. The objective of this study was to compare survival outcomes for patients who were staged according to the 1988 FIGO staging system versus the 2009 FIGO staging system.

METHODS:

Data were obtained from the Surveillance, Epidemiology, and End Results Program for the years 1998 to 2006. Patients who had a diagnosis of adenocarcinoma of the uterus with complete staging information were included. Patients were staged according to the 1988 and 2009 FIGO staging systems, and Kaplan‐Meier estimates were derived for cause‐specific survival (CSS). Univariate and multivariate analyses using Cox proportional hazards models were used to identify the factors associated with survival.

RESULTS:

In total, 47,284 patients were included. The median follow‐up was 37 months. The 5‐year CSS rates for patients who had 2009 FIGO stage IA and IB disease were 96.6% and 89.9%, respectively (P < .0001). After accounting for age, grade, and race, this survival difference remained significant (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.74‐2.24; P < .0001). Patients who had 1988 FIGO stage IIA disease had a 5‐year CSS rate similar to that of patients who had 1988 FIGO stage IC disease (88.6% vs 89.9%, respectively; P = .09). Patients who had positive pelvic washings had a 5‐year CSS rate similar to that of patients who had stage IIIA disease according to the 2009 FIGO system (74.2% vs 72.1%, respectively; P = .37). The 5‐year CSS rate for patients who had stage IIIC1 disease was significantly improved compared with that for patients who had stage IIIC2 disease (68.2% vs 57.3%, respectively; P < .0001). In the multivariate model, the survival difference remained (HR, 1.49; 95% CI, 1.26‐1.76; P < .0001).

CONCLUSIONS:

The 2009 staging system for endometrial cancer produced better discrimination in CSS outcomes compared with the 1988 system. Cancer 2011;. © 2011 American Cancer Society.     

Intensity-modulated radiation therapy versus conventional radiation therapy for squamous cell carcinoma of the anal canal

BACKGROUND:

The purpose of this study was to compare outcomes in patients with anal canal squamous cell carcinoma (SCCA) who were treated with definitive chemoradiotherapy by either intensity‐modulated radiation therapy (IMRT) or conventional radiotherapy (CRT).

METHODS:

Forty‐six patients who received definitive chemoradiotherapy from January 1993 to August 2009 were included. Forty‐five patients received 5‐fluorouracil with mitomycin C (n = 39) or cisplatin (n = 6). Seventeen (37%) were treated with CRT and 29 (63%) with IMRT. The median dose was 54 Gy in both groups. Median follow‐up was 26 months (CRT) and 32 months (IMRT). T3‐T4 stage (P = .18) and lymph node‐positive disease (P = .6) were similar between groups.

RESULTS:

The CRT group required longer treatment duration (57 days vs 40 days, P < .0001), more treatment breaks (88% vs 34.5%, P = .001), and longer breaks (12 days vs 1.5 days, P < .0001) than patients treated with IMRT. Eleven (65%) patients in the CRT group experienced grade >2 nonhematologic toxicity compared with 6 (21%) patients in the IMRT group (P = .003). The 3‐year overall survival (OS), locoregional control (LRC), and progression‐free survival were 87.8%, 91.9%, and 84.2%, respectively, for the IMRT groups and 51.8%, 56.7%, and 56.7%, respectively, for the CRT group (all P < .01). On multivariate analysis, T stage, use of IMRT, and treatment duration were associated with OS, and T stage and use of IMRT were associated with LRC.

CONCLUSIONS:

The use of IMRT was associated with less toxicity, reduced need for treatment breaks, and excellent LRC and OS compared with CRT in patients with SCCA of the anal canal. Cancer 2011. © 2011 American Cancer Society.     

Cuplike nuclei (prominent nuclear invaginations) in acute myeloid leukemia are highly associated with FLT3 internal tandem duplication and NPM1 mutation

BACKGROUND:

A small subset of patients with acute myeloid leukemia (AML) have cuplike nuclei. Other investigators have demonstrated that these neoplasms have distinctive clinicopathologic and molecular features.

METHODS:

The authors searched for patients who had AML with cuplike nuclei at their institution over a 10‐year interval. A strict definition for cuplike nuclei was used: ≥10% blasts with nuclear invaginations in ≥25% of the nuclear area. The relevant data were reviewed, and the results were compared with a control group of patients who had AML without cuplike nuclei.

RESULTS:

In total, 22 patients who had AML with cuplike nuclei were identified and were classified as AML without maturation (French‐American‐British classification M1) (AML M1). Compared with the control group (AML M1), patients who had AML with cuplike nuclei were associated significantly with fms‐like tyrosine kinase 3 (FLT3)‐internal tandem duplication (ITD) (86% vs 38%, respectively; P = .002); nucleophosmin 1 (NPM1) mutations (86% vs 19%; P < .0001); both mutations (77% vs 14%; P < .0001); normal karyotype (86% vs 40%; P = .003); bone marrow blast count (90% vs 84%; P = .016); myeloperoxidase positivity (95% vs 30% blasts; P = .001); higher D‐dimer levels (>5000 ng/mL vs 569 ng/mL; P = .001); and the absence of CD7 (91% vs 52%; P = .007), CD34 (82% vs 5%; P < .0001), and human leukocyte antigen, D‐related (59% vs 10%; P = .001). There were no differences in age, sex, or peripheral blood counts. The positive predictive value of recognizing AML with cuplike nuclei for FLT3‐ITD, NPM1, and both mutations was 81%, 86%, and 77%, respectively.

CONCLUSIONS:

Cuplike nuclei in AML were highly associated with the presence of NPM1 and FLT3‐ITD mutations and with several clinicopathologic and immunophenotypic features. Recognition of the distinctive morphologic features of AML with cuplike nuclei may be helpful in streamlining the workup of these neoplasms. Cancer 2009. © 2009 American Cancer Society.     

Time for reappraisal of extracranial treatment options?

BACKGROUND.

The optimal treatment of the primary tumor in patients with brain metastases (BM) from newly diagnosed nonsmall cell lung cancer (NSCLC) remains unclear. The authors aimed to identify patient groups with synchronous BM for whom radical treatment of the primary site may be appropriate.

METHODS.

The medical records of 167 patients treated at our center between November 2000 and June 2009 for newly diagnosed NSCLC and synchronous BM were reviewed. All patients underwent surgery/radiosurgery (n = 86) or whole‐brain radiotherapy (WBRT; n = 81) for BM. Univariate and multivariate analyses assessed prognostic factors significant for overall survival (OS).

RESULTS.

Median OS of patients undergoing surgery/radiosurgery for BM was 12.1 months. Those undergoing “radical” thoracic treatment (n = 24) had a longer median OS (28.4 months) than those undergoing chemotherapy (n = 74; 12.1 months) or supportive therapy (n = 69; 5.6 months, P < .01). Patients with stage I thoracic disease (n = 23) had a longer median OS (18.5 months) than those with stage III (n = 43; 9.4 months) or with intra/extra‐thoracic metastases other than BM (stage IV; n = 20; 2.7 months, P < .01). Median OS of WBRT patients was 3.7 months. One patient underwent radical thoracic treatment. Patients undergoing chemotherapy (n = 42) had a longer median OS (5.7 months) than patients undergoing supportive therapy only (n = 38; 1.6 months, P < .01). Performance status and age were also associated with OS.

CONCLUSIONS.

Radical thoracic treatments may be justified in selected patients <65‐years‐old, eligible to undergo surgery/radiosurgery for synchronous BM from NSCLC, even when stage III thoracic disease is present. Cancer 2011. © 2010 American Cancer Society     

Percutaneous radiofrequency ablation of painful osseous metastases

BACKGROUND:

The study was conducted to determine whether radiofrequency ablation (RFA) can safely reduce pain from osseous metastatic disease.

METHODS:

The single‐arm prospective trial included patients with a single painful bone metastasis with unremitting pain with a score >50 on a pain scale of 0‐100. Percutaneous computed tomography‐guided RFA of the bone metastasis to temperatures >60°C was performed. Endpoints were the toxicity and pain effects of RFA before and at 2 weeks, 1 month, and 3 months after RFA.

RESULTS:

Fifty‐five patients completed RFA. Grade 3 toxicities occurred in 3 of 55 (5%) patients. RFA reduced pain at 1 and 3 months for all pain assessment measures. The average increase in pain relief from pre‐RFA to 1‐month follow‐up is 26.3 (95% confidence interval [CI], 17.7‐34.9; P < .0001), and the increase from pre‐RFA to 3‐month follow‐up is 16.38 (95% CI, 3.4‐29.4; P = .02). The average decrease in pain intensity from pre‐RFA to 1‐month follow‐up was 26.9 (P < .0001) and 14.2 for 3‐month follow‐up (P = .02). The odds of lower pain severity at 1‐month follow‐up were 14.0 (95% CI, 2.3‐25.7; P < .0001) times higher than at pre‐RFA, and the odds at 3‐month follow‐up were 8.0 (95% CI, 0.9‐15.2; P < .001) times higher than at pre‐RFA. The average increase in mood from pre‐RFA to 1‐month follow‐up was 19.9 (P < .0001) and 14.9 to 3‐month follow‐up (P = .005).

CONCLUSIONS:

This cooperative group trial strongly suggests that RFA can safely palliate pain from bone metastases. Cancer 2010. © 2010 American Cancer Society