Methadone initiation and rotation in the outpatient setting for patients with cancer pain

BACKGROUND:

Methadone is an effective and inexpensive opioid for cancer pain treatment. It has been reported as difficult to use in the outpatient setting because of its variable relative potency and long half‐life. The purpose of this study was to determine the outcome of methadone initiation or rotation for cancer pain treatment in outpatient settings.

METHODS:

Chart review was done of 189 consecutive patients who underwent methadone initiation or rotation at the authors' palliative care outpatient center. Data were collected regarding demographic and clinical characteristics, symptoms, and opioid side effects at baseline and for 2 follow‐up visits (F1, F2). Failure was defined as methadone discontinuation by the palliative care physician or patient's hospitalization for uncontrolled pain or methadone‐related side effects at F1.

RESULTS:

One hundred (53%) initiations and 89 (47%) rotations were conducted. Success rates for methadone initiation and rotation were 82 of 89 (92%) and 85 of 100 (84%), respectively. Mean (standard deviation) age was 60 (11) years. One hundred (53%) patients were women, 138 (73%) were white, and 182 (96%) had solid cancers. The main reason for rotation was pain (65 of 89 patients, 47%). Median (interquartile range, IQR) pain scores (Edmonton Symptom Assessment Scale/0‐10) were 6 (5‐8), 4 (3‐6), and 3 (2‐5) at baseline, F1, and F2, respectively (P < .0001). Median (IQR) daily methadone dose for initiation and rotation was 10 (5‐15) mg and 15 (10‐30) mg at F1 (P < .0001) and 10 (8‐15) mg and 18 (10‐30) mg at F2 (P < .0001), respectively. Constipation and nausea improved (P < .005) after initiation/rotation to methadone. Frequency of sedation, hallucinations, myoclonus, and delirium did not increase after initiation/rotation to methadone.

CONCLUSIONS:

Outpatient methadone initiation and rotation for cancer pain treatment were safe, with high success rates and low side effect profiles. Cancer 2010. © 2010 American Cancer Society.     

Cryoablation or radiofrequency ablation of the small renal mass : a meta-analysis

BACKGROUND.

The incidence of renal cell carcinoma is rising because of incidental detection of small renal masses (SRMs). Although surgical resection remains the standard of care, cryoablation and radiofrequency ablation (RFA) have emerged as minimally invasive treatment alternatives. The authors of this report performed a comparative meta‐analysis evaluating cryoablation and RFA as primary treatment for SRMs.

METHODS.

A search of the MEDLINE database was performed reviewing the world literature for clinically localized renal masses treated by cryoablation or RFA.

RESULTS.

Forty‐seven studies representing 1375 kidney lesions treated by cryoablation or RFA were analyzed. No differences were detected between ablation modalities with regard to mean patient age (P = .17), tumor size (P = .12), or duration of follow‐up (P = .53). Pretreatment biopsy was performed more often for cryoablated lesions (82.3%) than for RFA (62.2%; P < .0001). Unknown pathology occurred at a significantly higher rate for SRMs that underwent RFA (40.4%) versus cryoablation (24.5%; P < .0001). Repeat ablation was performed more often after RFA (8.5% vs 1.3%; P < .0001), and the rates of local tumor progression were significantly higher for RFA (12.9% vs 5.2%; P < .0001) compared with cryoablation. The higher incidence of local tumor progression was found to be correlated significantly with treatment by RFA on univariate analysis (P = .001) and on multivariate regression analysis (P = .003). Metastasis was reported less frequently for cryoablation (1.0%) versus RFA (2.5%; P = .06). Cryoablation usually was performed laparoscopically (65%), whereas 94% of lesions that were treated with RFA were approached percutaneously.

CONCLUSIONS.

Ablation of SRMs is a viable strategy based on short‐term oncologic outcomes. Although extended oncologic efficacy remains to be established for ablation modalities, the current data suggest that cryoablation results in fewer retreatments and improved local tumor control, and it may be associated with a lower risk of metastatic progression compared with RFA. Cancer 2008. © 2008 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     

An Effective Therapy to Painful Bone Metastases: Cryoablation Combined with Zoledronic Acid

Approximately half or more of patients diagnosed with late malignant tumors may suffer from metastatic bone pain, effective palliation of pain becomes an important part of comprehensive therapy for malignant tumors. In this study, we examined the efficacy and safety of the combined regimen of cryoablation and zoledronic acid in patients of bone metastatic pain. A total of 84 subjects were randomly divided into three groups, and underwent treatments of cryoablation plus zoledronic acid, cryoablation alone, zoledronic acid alone between June 2009 and March 2012. Patients responses had been assessed for a total of 6 months by using the Brief Pain Inventory (BPI)-Short Form. The results showed that the mean response of worst and average pain significantly dropped at week 2 (all P?P?P?Cryoablation plus zoledronic acid regimen showed significant drop in worst and average pain between week 1 and week 4 compared to zoledronic acid alone (all P?P?相似文献   

A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer

BACKGROUND:

A recent randomized trial to compare external beam radiation therapy (EBRT) to cryoablation for localized disease showed cryoablation to be noninferior to external beam EBRT in disease progression and overall and disease‐specific survival. We report on the quality of life (QOL) outcomes for this trial.

METHODS:

From December 1997 through February 2003, 244 men with newly diagnosed localized prostate cancer were randomly assigned to cryoablation or EBRT (median dose 68 Gy). All patients received neoadjuvant antiandrogen therapy. Patients completed the EORTC QLQ C30 and the Prostate Cancer Index (PCI) before treatment and at 1.5, 3, 6, 12, 18, 24, and 36 months post‐treatment.

RESULTS:

Regardless of treatment arm, participants reported high levels of QOL with few exceptions. cryoablation was associated with more acute urinary dysfunction (mean PCI urinary function cryoablation = 69.4; mean EBRT = 90.7; P < .001), which resolved over time. No late arising QOL issues were observed. Both EBRT and cryoablation participants reported decreases in sexual function at 3 months with the cryoablation patients reporting poorer functioning (mean cryoablation = 7.2: mean EBRT = 32.9; P < .001). Mean sexual function score was 15 points lower at 3 years for the cryoablation group and 13% more of the cryoablation men said that sexuality was a moderate or big problem.

CONCLUSIONS:

In this randomized trial, no long‐term QOL advantage for either treatment was apparent with the exception of poorer sexual function reported by those treated with cryoablation. Men who wish to increase their odds of retaining sexual function might be counseled to choose EBRT over cryoablation. Cancer 2009. © 2009 American Cancer Society.     

Characteristics of patients who refuse do‐not‐resuscitate orders upon admission to an acute palliative care unit in a comprehensive cancer center

BACKGROUND:

Refusal of appropriately indicated do‐not‐resuscitate (DNR) orders may cause harm and distress for patients, families, and the medical team. We conducted a retrospective study to determine the frequency and predictors of refusals of DNR in advanced cancer patients admitted to an acute palliative care unit.

METHODS:

A total of 2538 consecutive admissions were reviewed. Demographic and clinical characteristics from 200 consecutive patients with DNR orders and 100 consecutive patients who refused DNR were collected, and differences between the groups were determined by multivariate regression and recursive partitioning analysis.

RESULTS:

Of 2538 admissions, 2530 (99%) were appropriate for DNR discussion. Of the 2530 admissions, 2374 were unique patients, and 100 (4%) of 2374 refused DNR. Refusers had median (interquartile range, IQR) pain of 7 (4‐9) versus 5 (3‐8, P = .0005), nausea of 2 (0‐7) versus 1 (0‐4, P = .05), and dyspnea of 1 (0‐5) versus 4 (0‐7, P = .002) as compared with DNR nonrefusers, respectively. Patients with hematological malignancies and advance directives had a lower DNR refusal risk (odds ratio [OR], 0.38; P = .02, and OR, 0.36; P < .0001, respectively). Multivariate regression analysis revealed that patients with moderate‐severe pain (OR, 3.19; P = .002) and with no advance directives (OR, 2.94; P ≤ .001) had higher DNR refusal risk. There were more inpatient deaths among DNR nonrefusers (87 of 200 vs 1 of 100, P < .0001). Median (IQR) time from discharge to death was 18 (8‐35) days for those with DNR orders and 85 (25‐206) days for DNR refusers (P ≤ .0001).

CONCLUSIONS:

DNR refusal in patients admitted to the acute palliative care unit is low, more frequent in patients with more pain and nausea and no advance directives, and associated with longer survival. This study demonstrates possible predictors of complicated DNR discussions. Cancer 2010. © 2010 American Cancer Society.     

Twenty‐four‐month postradiation prostate biopsies are strongly predictive of 7‐year disease‐free survival

BACKGROUND:

The objective of this study was to evaluate the predictive value of prostate biopsies that were obtained 24 months after the completion of radiotherapy (RT) with respect to disease‐free survival (DFS) in a randomized trial that compared 3 months versus 8 months of neoadjuvant hormone therapy before conventional dose external RT.

METHODS:

From February 1995 to June 2001, 378 men were randomized to receive either 3 months or 8 months of combined flutamide and goserelin before they received 66 Gray of RT at 4 participating centers. By risk group, 26% of patients were categorized as low risk, 43% were categorized as intermediate risk, and 31% were categorized as high risk. The 2 treatment arms were balanced in terms of age, Gleason score, clinical tumor classification, risk group, and presenting prostate‐specific antigen level. The median follow‐up for the patients who remained alive was 6.6 years (range, 1.6‐10.1 years). Of 361 evaluable patients, 290 patients remained alive. Post‐RT prostate biopsies were performed between 24 and 30 months after the completion of RT in 3 of the 4 centers. Biopsies that had residual tumor with severe treatment effect were considered indeterminate, and biopsies that had minimal or no treatment effect were considered positive.

RESULTS:

The 5‐year rate of actuarial freedom from any failure for the 3‐month arm versus the 8‐month arm was 72% versus 75% (P = .18). The DFS for patients who had negative and indeterminate biopsies was similar. Two‐year post‐treatment biopsy status was a strong predictor of 5‐year DFS rate (82% and 83% for negative and indeterminate biopsies, respectively, vs 27% for positive biopsies; P < .0001). Multivariate analysis indicated that biopsy status (P < .0001) and Gleason score (P < .0001) were the strongest determinates of biochemical DFS.

CONCLUSIONS:

Two‐year post‐RT prostate biopsies were strongly predictive of subsequent DFS. Biopsies with severe treatment effect were considered negative. Cancer 2009. © 2008 American Cancer Society.     

Pain outcomes in patients with advanced breast cancer and bone metastases

BACKGROUND:

In this study, the authors evaluated the effect of denosumab versus zoledronic acid (ZA) on pain in patients with advanced breast cancer and bone metastases.

METHODS:

The prevention of pain, reduction in pain interference with daily life activities, and the proportion of patients requiring strong opioid analgesics were assessed in a randomized, double‐blind, double‐dummy phase 3 study comparing denosumab with ZA for preventing skeletal‐related events in 2046 patients who had breast cancer and bone metastases. Patients completed the Brief Pain Inventory‐Short Form at baseline and monthly thereafter.

RESULTS:

Fewer patients who received denosumab reported a clinically meaningful worsening of pain severity (≥2‐point increase) from baseline compared with patients who received ZA, and a trend was observed toward delayed time to pain worsening with denosumab versus ZA (denosumab, 8.5 months; ZA, 7.4 months; P = .08). In patients who had no/mild pain at baseline, a 4‐month delay in progression to moderate/severe pain was observed with denosumab compared with ZA (9.7 months vs 5.8 months; P = .002). Denosumab delayed the time to increased pain interference by approximately 1 month compared with ZA (denosumab, 16.0 months; ZA, 14.9 months; P = .09). The time to pain improvement (P = .72) and the time to decreased pain interference (P = .92) were similar between the groups. Fewer denosumab‐treated patients reported increased analgesic use from no/low use at baseline to strong opioid use.

CONCLUSIONS:

Denosumab demonstrated improved pain prevention and comparable pain palliation compared with ZA. In addition, fewer denosumab‐treated patients shifted to strong opioid analgesic use. Cancer 2013. © 2012 American Cancer Society.     

Prognostic factors derived from a prospective database dictate clinical biology of anal cancer

BACKGROUND:

Only 4 prospective randomized phase 3 trials have been reported for anal cancer. A prognostic factor analysis for anal cancer from a prospective database has been published from only 1 study (N = 110). To confirm and uncover new prognostic factors, we analyzed the prospective database of intergroup RTOG 98‐11.

METHODS:

Univariate and multivariate analyses of the baseline characteristics for 5‐year overall survival (OS) and disease‐free survival (DFS) were carried out. Various combinations of tumor diameter and clinically positive nodes (N⁺) were analyzed to identify subgroups.

RESULTS:

A total of 644 were assessable and analyzed. Tumor diameter >5 cm was associated with poorer 5‐year DFS (P = .0003) and poorer 5‐year OS (P = .0031), and N⁺ was associated with poorer 5‐year DFS (P ≤ .0001) and poorer 5‐year OS (P = ≤ .0001) in the multivariate analysis. In stratified analyses, N⁺ had more adverse influence on DFS and OS than did tumor diameter. Patients with >5‐cm tumor and N⁺ had the worst DFS (only 30% at 3 years compared with 74% for the best group; <5 cm primary and N0) and OS (only 48% at 4 years compared with 81% for the best group; <5 cm primary and N0). Men had worse DFS (P = .02) and OS (P = .016). These factors maintained their influence in each treatment arm.

CONCLUSIONS:

This prospective prognostic factor analysis establishes tumor diameter as an independent prognosticator of poorer 5‐year DFS and OS and confirms N⁺ and male sex as poor prognostic factors. This analysis also uncovers novel subgroups (derived from combining prognostic factors) with incremental worsening of DFS and OS. Cancer 2010. © 2010 American Cancer Society.     

Breast cancer subtypes and response to systemic treatment after whole‐brain radiotherapy in patients with brain metastases

BACKGROUND:

The aim of this study was to assess the role of systemic treatment after whole‐brain radiotherapy (WBRT) in immunohistochemically defined biological subsets of breast cancer patients with brain metastases.

METHODS:

The group of 420 consecutive breast cancer patients with brain metastases treated at the same institution between the years of 2003 to 2009 was analyzed. Patients were divided into 4 immunohistochemically biological subsets, based on the levels of estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) receptors, and labeled as luminal A, luminal B, HER2, and triple‐negative. Survival from brain metastases with and without systemic treatment after WBRT was calculated in 4 subsets.

RESULTS:

In the entire group, the median survival from brain metastases in patients without and with systemic treatment after WBRT was 3 and 10 months, respectively (P < .0001). In the triple‐negative subset, the median survival from brain metastases with and without systemic treatment was 4 and 3 months (P = .16), and in the luminal A subset, it was 12 and 3 months, respectively (P = .003). In the luminal B subset, the median survival without further treatment, after chemotherapy and/or hormonal therapy, and after chemotherapy and/or hormonal therapy with targeted therapy was 2 months, 9 months, and 15 months, respectively (P < .0001). In the HER2 subset, the median survival was 4 months, 6 months, and 13 months, respectively (P < .0001). No significant response to systemic treatment was noted in the triple‐negative breast cancer population.

CONCLUSIONS:

Systemic therapy, ordered after WBRT, appears to improve survival in patients with the luminal A, luminal B, and HER2 breast cancer subtypes. Targeted therapy was found to have an additional positive impact on survival. In patients with triple‐negative breast cancer, the role of systemic treatment after WBRT appears to be less clear, and therefore this issue requires further investigation. Cancer 2010. © 2010 American Cancer Society.     

Cytomorphologic features of poorly differentiated thyroid carcinoma

BACKGROUND:

Poorly differentiated thyroid carcinoma (PDTC) is an uncommon and aggressive malignancy. Despite the significant clinical implications of a diagnosis of PDTC, its cytomorphologic features have not been well defined. Statistical analysis was applied to a series of 40 PDTCs to identify a specific set of cytomorphologic features that characterized these tumors on fine‐needle aspiration biopsy (FNAB).

METHODS:

In total, 40 thyroid FNABs that were highly diagnosed histologically as PDTC (19 insular carcinomas and 21 noninsular carcinomas) comprised the study group. A control group of 40 well differentiated thyroid neoplasms were selected for comparison. All FNABs were reviewed and scored for a series of 32 cytomorphologic features. The results were evaluated using univariate and stepwise logistic regression (SLR) analyses.

RESULTS:

In univariate analysis, 17 cytomorphologic features were identified that characterized the 40 PDTCs: insular, solid, or trabecular cytoarchitecture (P < .001); high cellularity (P = .007); necrosis (P = .025) or background debris (P = .025); plasmacytoid appearance (P = .0007); single cells (P < .0001); high nuclear/cytoplasmic ratio (P < .0001); scant cytoplasm (P = .03); nuclear atypia (P < .0001), including nuclear pleomorphism (P = .0052) and anisokaryosis (P < .0001); granular/coarse chromatin (P = .026); naked nuclei (P = .01); mitotic activity (P = .0001) and apoptosis (P < .0001); endothelial wrapping (P = .0053); and severe crowding (P < .0001). In logistic regression analysis, severe crowding (P = .0008) and cytoarchitecture (P < .0001) were identified as the most significant cytomorphologic features of PDTCs, and the combination of cytoarchitecture, severe crowding, single cells, and high nuclear/cytoplasmic ratio was the most predictive of PDTC.

CONCLUSIONS:

PDTCs have characteristic cytomorphologic features. By using logistic regression analysis, the features that were identified as the most predictive of PDTC were severe crowding, insular/solid/trabecular morphology, single cells, and high nuclear/cytoplasmic ratio. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.     

Elective irradiation of pelvic lymph nodes during postprostatectomy salvage radiotherapy

BACKGROUND:

Success rates with salvage radiotherapy (SRT) in men who have a postprostatectomy biochemical relapse are suboptimal. One treatment‐intensification strategy includes elective irradiation of the pelvic lymph nodes with whole pelvis radiotherapy (WPRT).

METHODS:

An inter‐institutional retrospective cohort study compared outcomes for patients who received SRT at 2 separate academic institutions with disparate treatment paradigms: almost exclusively favoring WPRT (n = 112) versus limiting treatment to the prostate bed (PBRT) (n = 135). Patients were excluded if they had lymph node involvement or if they received androgen‐deprivation therapy. The Cox proportional hazards model was used to adjust for potential confounders.

RESULTS:

In total, 247 patients were analyzed with a median follow‐up of 4 years. The pre‐SRT prostate‐specific antigen (PSA) level (adjusted hazard ratio [HR], 1.58; P < .0001) and a Gleason score of 8 to 10 (adjusted HR, 3.21; P < .0001) were identified as independent predictors of increased risk of biochemical PSA progression after SRT. However, WPRT was not independently associated with biochemical progression‐free survival in the multivariate model (adjusted HR, 0.79; P = .20). Neither low‐risk patients nor high‐risk patients (defined a priori by a preoperative PSA level ≥20 ng/mL, a pathologic Gleason score between 8 and 10, or pathologic T3 tumor classification) benefited from WPRT. Overall survival was similar between treatment groups. When restricting the analysis to patients with pre‐SRT PSA levels ≥0.4 ng/mL (n = 139), WPRT was independently associated with a 53% reduction in the risk of biochemical progression (adjusted HR, 0.47; P = .031).

CONCLUSIONS:

WPRT did not improve outcomes among the entire group but was independently associated with improved biochemical control among patients with pre‐SRT PSA levels ≥0.4 ng/mL. Cancer 2013. © 2012 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.     

Mortality increases when radical cystectomy is delayed more than 12 weeks

BACKGROUND:

Single‐institution series have documented the adverse impact of a 12‐week delay between resection of muscle‐invasive bladder cancer and radical cystectomy. These data are derived from tertiary centers, in which referral populations may confound outcomes. The authors sought to examine the survival impact of a delay in radical cystectomy using nationally representative data.

METHODS:

From the linked Surveillance, Epidemiology, and End Results–Medicare dataset, the authors identified subjects with stage II transitional cell carcinoma (TCC) of the bladder who underwent radical cystectomy between 1992 and 2001. They examined delays of 8, 12, and 24 weeks and incorporated these delay cutoffs into multivariate Cox proportional hazards survival models. Covariates included age, race/ethnicity, marital status, Charlson comorbidity index, and cancer grade.

RESULTS:

The authors identified 441 subjects with stage II TCC who underwent cystectomy during the study period. Compared with immediate surgery (ie, within 4‐8 weeks of transurethral resection), longer time to cystectomy increased the risk of both disease‐specific and overall mortality (hazard ratio [HR], 2.0; P < .01 and HR, 1.6; P < .01, respectively, for those delayed 12‐24 weeks; HR, 2.0; P < .01 for disease‐specific and overall death among those delayed beyond 24 weeks 1 year after diagnosis). Covariates associated with overall mortality included older age (HR, 1.04; P < .01) and comorbidity (HR, 2.0 for Charlson ≥3 vs Charlson 0‐1; P < .01).

CONCLUSIONS:

Delay in definitive surgical treatment beyond 12 weeks conferred an increased risk of disease‐specific and all‐cause mortality among subjects with stage II bladder cancer. Cancer 2009. © 2009 American Cancer Society.     

Driver mutations determine survival in smokers and never‐smokers with stage IIIB/IV lung adenocarcinomas

BACKGROUND:

The authors previously demonstrated that never‐smokers with stage IIIB/IV nonsmall cell lung cancer (NSCLC) lived 50% longer than former/current smokers. This observation persisted after adjusting for age, performance status, and sex. In this study, the authors hypothesized that smoking‐dependent differences in the distribution of driver mutations may explain differences in prognosis between these subgroups.

METHODS:

In total, 293 never‐smokers and 382 former/current smokers with lung adenocarcinoma who underwent testing for epidermal growth factor receptor (EGFR) mutations and v‐Ki‐ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and rearrangements in anaplastic lymphoma kinase (ALK) between 2009 and 2010 were investigated. Clinical outcomes and patient characteristics were collected. Survival probabilities were estimated using the Kaplan‐Meier method. Group comparison was performed with log‐rank tests and Cox proportional hazards methods.

RESULTS:

Although the overall incidence of these mutations was nearly identical (55% never‐smokers vs 57% current/former smokers; P = .48), there were significant differences in the distribution of mutations between these groups for EGFR mutations (37% never‐smokers vs 14% former/current smokers; P < .0001), KRAS mutations (4% never‐smokers vs 43% former/current smokers; P < .0001), and ALK rearrangements (12% never‐smokers vs 2% former/current smokers; P < .0001). Among never‐smokers and former/current smokers, the prognosis differed significantly by genotype. Patients who had KRAS mutations had the poorest survival. Smoking status, however, had no influence on survival within each genotype.

CONCLUSIONS:

Never‐smokers and former/current smokers with lung adenocarcinomas were not homogeneous subgroups. Each was made up of individuals whose tumors had a unique distribution of driver mutations, which were associated with different prognoses, irrespective of smoking history. Cancer 2012. © 2012 American Cancer Society.     

Randomized trial of paclitaxel versus pegylated liposomal doxorubicin for advanced human immunodeficiency virus‐associated Kaposi sarcoma

BACKGROUND:

Paclitaxel and pegylated liposomal doxorubicin (PLD) are active cytotoxic agents for the treatment of human immunodeficiency virus (HIV)‐associated Kaposi sarcoma (KS). A randomized trial comparing the efficacy and toxicity of paclitaxel and PLD was performed, and the effects of therapy on symptom palliation and quality of life were determined.

METHODS:

Patients with advanced HIV‐associated KS were randomly assigned to receive paclitaxel at a dose of 100 mg/m² intravenously (iv) every 2 weeks or PLD at a dose of 20 mg/m² iv every 3 weeks. The KS Functional Assessment of HIV (FAHI) quality of life instrument was used before and after every other treatment cycle.

RESULTS:

The study included 73 analyzable patients enrolled between 1998 and 2002, including 36 in the paclitaxel arm and 37 in the PLD arm; 73% of patients received highly active antiretroviral therapy (HAART) and 32% had an undetectable viral load (<400 copies/mL). Treatment was associated with significant improvements in pain (P = .024) and swelling (P < .001). Of the 36 patients who reported that pain interfered with their normal work or activities at baseline, 25 (69%) improved. Of the 41 patients who reported swelling at baseline, 38 (93%) improved. Comparing the paclitaxel and PLD arms revealed comparable response rates (56% vs 46%; P = .49), median progression‐free survival (17.5 months vs 12.2 months; P = .66), and 2‐year survival rates (79% vs 78%; P = .75), but somewhat more grade 3 to 5 toxicity for paclitaxel (84% vs 66%; P = .077).

CONCLUSIONS:

Treatment with either paclitaxel or PLD appears to produce significant improvements in pain and swelling in patients with advanced, symptomatic, HIV‐associated KS treated in the HAART era. Cancer 2010. © 2010 American Cancer Society.     

Extent of disease burden determined with magnetic resonance imaging of the bone marrow is predictive of survival outcome in patients with multiple myeloma

BACKGROUND:

Multiple myeloma (MM) remains an incurable cancer. Treatment often is initiated at the time patients experience a progressive increase in tumor burden. The authors of this report investigated magnetic resonance imaging of the bone marrow (BM‐MRI) as a novel approach to quantify disease burden and validated a staging system by correlating BM‐MRI with common clinical and laboratory parameters.

METHODS:

The extent of bone marrow involvement was evaluated by BM‐MRI. Clinical and laboratory parameters were assessed in patients with active MM, and correlations between variables were assessed statistically. Bone marrow involvement by BM‐MRI was defined as stage A (0%), stage B (<10%), stage C (10%‐50%), and stage D (>50%).

RESULTS:

In total, 170 consecutive patients were evaluated (77 women and 93 men), including 144 patients who had active MM. The median age was 61 years (age range, 35‐83 years). Advance stage disease (stage >I) based on Durie‐Salmon (DS) staging or International Staging System (ISS) criteria was observed in 122 patients (84%) and 77 patients (53%), respectively. Lytic bone disease was noted in 120 patients (83%). There was a significant association between BM‐MRI involvement and DS stage (P = .0006), ISS stage (P = .0001), the presence of lytic bone disease (P < .0001) and mean β‐2 microglobulin levels (P < .0001). Among the patients with previously untreated MM, there was a significant association between BM‐MRI stage and overall survival (OS) (univariate P = .013; multivariate P = .045). Plasmacytosis on bone marrow biopsy at diagnosis was not predictive of OS (P = .91).

CONCLUSIONS:

BM‐MRI is a novel approach for quantifying disease burden in patients with MM. The current investigation in a large cohort of nontransplantion MM patients demonstrated that the extent of bone marrow involvement determined by BM‐MRI correlates accurately with other conventional parameters of disease burden and can independently predict survival in patients with MM at the time of initial diagnosis. Cancer 2010. © 2010 American Cancer Society.     

Breast cancer in men in the United States

BACKGROUND:

Breast cancer in men is rare, so clinical trials are not practical. Recommendations suggest treating men who are diagnosed with breast cancer using the guidelines for postmenopausal women; however, to date, no population‐based studies have evaluated patterns of care.

METHODS:

To examine characteristics, treatment, and survival among men with newly diagnosed breast cancer, in 2003 and 2004, 512 men were identified from the Surveillance, Epidemiology and End Results Program. Data were reabstracted and therapy was verified through the patients' treating physicians.

RESULTS:

The majority of men (79%) were diagnosed through discovery of a breast lump or other signs/symptoms. Among men who had invasive disease, 86% underwent mastectomy, 37% received chemotherapy, and 58% received hormone therapy. In multivariate analysis, tumor size (P = .01) and positive lymph node status (P < .0001) were associated positively with the use of chemotherapy, whereas age group (P < .0001) and current unmarried status (P = .01) had negative associations. Among men who had invasive, estrogen receptor (ER)‐positive/borderline tumors, the use of tamoxifen or aromatase inhibitors (AIs) was associated with age group (P = .05). Among men who had invasive disease, cancer mortality was associated with tumor size (P < .0001). Among men with ER‐positive/borderline disease, increased cancer mortality was associated with tumor size (P < .0001), current unmarried status (P = .04), and decreased mortality with tamoxifen (P = .04).

CONCLUSIONS:

Tumor characteristics and marital status were the primary predictors of therapy and cancer mortality among men with breast cancer. Although AIs are not currently recommended, they are commonly prescribed. However, their use did not result in a decrease in cancer mortality. Research must examine the efficacy of AIs with and without gonadotropin‐releasing hormone analogues. Cancer 2010. © 2010 American Cancer Society.     

Outcome and prognostic features in pediatric gliomas

BACKGROUND:

Pediatric gliomas are rare and heterogeneous tumors. The Surveillance, Epidemiology, and End Results (SEER) database allows a large‐scale analysis of the clinical characteristics and prognostic features of these tumors.

METHODS:

The authors analyzed available SEER data on 6212 patients younger than 20 years at diagnosis of glioma (1973‐2005), according to 4 age categories: <1 year, 1‐3 years, 3‐5 years, and 5‐20 years.

RESULTS:

The overall 5‐ and 10‐year survival estimates were 71% ± 0.62% (standard error) and 68% ± 0.67%, respectively. Forty‐one percent of gliomas were cerebral; the frequency of cerebellar tumors (22%‐32% of gliomas) increased sharply after the first year of life. Of the tumors for which grade was available, 77% were low grade (grade I or II). Tumor grade emerged as the most significant independent prognostic factor in all age groups except the youngest age group, in which extent of resection was most significant. Surgery other than gross total resection was an adverse prognostic factor (hazard ratio, 2.18; 95% confidence interval, 1.78‐2.67). Age <3 years predicted a greater likelihood of survival in patients with high‐grade gliomas and brainstem tumors. Conversely, age <3 years predicted a lower likelihood of survival in patients with low‐grade gliomas. Children aged <1 year received less radiotherapy than older patients (P < .0001) and were less likely to undergo gross total resection (P < .0001).

CONCLUSIONS:

The survival of children with gliomas is influenced by histologic subtype, age, and extent of resection. Despite its limitations, the SEER database provides a useful tool for studies of rare tumors such as pediatric gliomas. Cancer 2009. © 2009 American Cancer Society.     

Does hormone treatment added to radiotherapy improve outcome in locally advanced prostate cancer?

BACKGROUND:

To quantify the magnitude of benefit of the addition of hormone treatment (HT) to exclusive radiotherapy for locally advanced prostate cancer, a literature‐based meta‐analysis was conducted.

METHODS:

Event‐based relative risks (RR) with 95% confidence intervals (CIs) were derived through a random‐effect model. Differences in primary (biochemical failure and clinical progression‐free survival) and secondary outcomes (cancer‐specific survival, overall survival [OS], recurrence patterns, and toxicity) were explored. Absolute differences and numbers of patients needed to treat (NNT) were calculated. A heterogeneity test, a metaregression analysis with clinical predictors of outcome, and a correlation analysis for surrogate endpoints were also performed.

RESULTS:

Seven trials (4387 patients) were gathered. Hormone suppression significantly decreased both biochemical failure (RR, 0.76; 95% CI, 0.70‐0.82; P < .0001) and clinical progression‐free survival (RR, 0.81; 95% CI 0.71‐0.93; P = .002), with absolute differences of 10% and 7.7%, respectively, which translates into 10 and 13 NNT. cancer‐specific survival (RR, 0.76; 95% CI, 0.69‐0.83; P < .0001) and OS (RR, 0.86; 95% CI, 0.80‐0.93; P < .0001) were also significantly improved by the addition of HT, without significant heterogeneity, with absolute differences of 5.5% and 4.9%, respectively, which translates into 18 and 20 NNT. Local and distant relapse were significantly decreased by HT, by 36% and 28%, respectively, and no significant differences in toxicity were found. Primary and secondary efficacy outcomes were significantly correlated.

CONCLUSIONS:

Hormone suppression plus radiotherapy significantly decreases recurrence and mortality of patients with localized prostate cancer, without affecting toxicity. Cancer 2009. © 2009 American Cancer Society.