Survival after second primary lung cancer: a population-based study of 187 Hodgkin lymphoma patients

BACKGROUND:

Lung cancer accounts for the largest absolute risk of second malignancies among Hodgkin lymphoma (HL) survivors. However, no population‐based studies have compared overall survival (OS) between HL survivors who developed nonsmall cell lung cancer (HL‐NSCLC) versus patients with first primary NSCLC (NSCLC‐1).

METHODS:

The authors compared the OS of 178,431 patients who had NSCLC‐1 and 187 patients who had HL‐NSCLC (among 22,648 HL survivors), accounting for sex, race, sociodemographic status, calendar year, and age at NSCLC diagnosis, and NSCLC histology and stage. All patients were reported to the population‐based Surveillance, Epidemiology, and End Results Program. Hazard ratios (HRs) were derived from a Cox proportional hazards model.

RESULTS:

Although the NSCLC stage distribution was similar in both groups (20% localized, 30% regional, and 50% distant), HL survivors experienced significantly inferior stage‐specific OS. For patients with localized, regional, and distant stage NSCLC, the HRs (95% confidence interval [CI]) for death among HL survivors were 1.60 (95% CI, 1.08‐2.37; P < .0001), 1.67 (95% CI, 1.26‐2.22; P = .0004), and 1.31 (95% CI, 1.06‐1.61; P = .013), respectively. Among HL‐NSCLC patients, significant associations were observed between more advanced NSCLC stage and the following variables: younger age at HL diagnosis (P = .003), younger age at NSCLC diagnosis (P = .048), and longer latency between HL and NSCLC diagnoses (P = .015).

CONCLUSIONS:

Compared with patients who had de novo NSCLC, HL survivors experienced a significant 30% to 60% decrease in OS after an NSCLC diagnosis. Further research is needed to not only elucidate the clinical‐biologic underpinnings of NSCLC after HL, including the influence of previous HL treatment, but also to define the role of lung cancer screening in selected patients. Cancer 2011;. © 2011 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.     

Salvage stereotactic radiosurgery for breast cancer brain metastases: outcomes and prognostic factors

BACKGROUND:

Salvage stereotactic radiosurgery (SRS) is often considered in breast cancer patients previously treated for brain metastases. The goal of this study was to analyze clinical outcomes and prognostic factors for survival in the salvage setting.

METHODS:

The authors retrospectively examined 79 consecutive breast cancer patients who received salvage SRS (interval of >3 months after initial therapy), 76 of whom (96%) received prior whole‐brain radiation therapy. Overall survival (OS) and central nervous system (CNS) progression‐free survival rates were calculated from the date of SRS using the Kaplan‐Meier method. Prognostic factors were evaluated using the Cox proportional hazards model.

RESULTS:

Median age was 50.5 years. Fifty‐eight percent of this population was estrogen receptor positive, 62% was HER2 positive, and 10% was triple negative. At the time of SRS, 95% had extracranial metastases, with 81% of extracranial metastases at other visceral sites (lung/pleura/liver). Forty‐eight percent had stable extracranial disease. Median interval from initial brain metastases therapy to SRS was 8.4 months. Median CNS progression‐free survival after SRS was 5.7 months (interquartile range [IQR], 3.6‐11 months), and median OS was 9.8 months (IQR, 3.8‐18 months). Eighty‐two percent of evaluable patients received further systemic therapy after SRS. HER2 status (adjusted hazard ratio [HR], 2.4; P = .008) and extracranial disease status (adjusted HR, 2.7; P = .004) were significant prognostic factors for survival on multivariate analysis.

CONCLUSIONS:

In patients with good Karnofsky performance status, salvage SRS for breast cancer brain metastases is a reasonable treatment option, given an associated median survival in excess of 9 months. Furthermore, patients with HER2‐positive tumors at diagnosis or stable extracranial disease at the time of SRS have an improved clinical course, with median survival of >1 year. Cancer 2012. © 2011 American Cancer Society.     

Long-term survival after radical prostatectomy versus external-beam radiotherapy for patients with high-risk prostate cancer

BACKGROUND:

The long‐term survival of patients with high‐risk prostate cancer was compared after radical prostatectomy (RRP) and after external beam radiation therapy (EBRT) with or without adjuvant androgen‐deprivation therapy (ADT).

METHODS:

In total, 1238 patients underwent RRP, and 609 patients received with EBRT (344 received EBRT plus ADT, and 265 received EBRT alone) between 1988 and 2004 who had a pretreatment prostate‐specific antigen (PSA) level ≥ 20 ng/mL, a biopsy Gleason score between 8 and 10, or clinical tumor classification ≥ T3. The median follow‐up was 10.2 years, 6.0 years, and 7.2 years after RRP, EBRT plus ADT, and EBRT alone, respectively. The impact of treatment modality on systemic progression, cancer‐specific survival, and overall survival was evaluated using multivariate Cox proportional hazard regression analysis and a competing risk‐regression model.

RESULTS:

The 10‐year cancer‐specific survival rate was 92%, 92%, and 88% after RRP, EBRT plus ADT, and EBRT alone, respectively (P = .06). After adjustment for case mix, no significant differences in the risks of systemic progression (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.51‐1.18; P = .23) or prostate cancer death (HR, 1.14; 95% CI, 0.68‐1.91; P = .61) were observed between patients who received EBRT plus ADT and patients who underwent RRP. The risk of all‐cause mortality, however, was greater after EBRT plus ADT than after RRP (HR, 1.60; 95% CI, 1.25‐2.05; P = .0002).

CONCLUSIONS:

RRP alone and EBRT plus ADT provided similar long‐term cancer control for patients with high‐risk prostate cancer. The authors concluded that continued investigation into the differing impact of treatments on quality‐of‐life and noncancer mortality will be necessary to determine the optimal management approach for these patients. Cancer 2011. © 2011 American Cancer Society.     

Impact of postoperative prostate‐specific antigen disease recurrence and the use of salvage therapy on the risk of death

BACKGROUND:

This report evaluated whether biochemical recurrence (BCR) as a time‐dependent covariate (t) after radical prostatectomy (RP) for prostate cancer was associated with the risk of death and whether salvage therapy with radiotherapy (RT) and/or hormonal therapy (HT) can lessen this risk

METHODS:

This was a retrospective cohort study of 3071 men who underwent RP at Duke University between 1988 and 2008 and had complete follow‐up data. A Cox regression multivariable analysis was used to determine whether BCR (t) was associated with the risk of death in men after adjusting for age, prostatectomy findings, and the use of salvage RT and/or HT.

RESULTS:

After a median follow‐up of 7.4 years, 546 (17.8%) men experienced BCR and 454 (14.8%) died. The median follow‐up after prostate‐specific antigen (PSA) failure was 11.2 years (interquartile range, 5.8‐16.0 years). BCR (t) was associated with an increased risk of death (adjusted hazards ratio [AHR], 1.03; 95% confidence interval [95% CI], 1.004‐1.06 [P = .025]). In men who experienced BCR, a PSA doubling time <6 months was associated with an increased risk of death (AHR, 1.55; 95% CI, 1.15‐2.1 [P = .004]); whereas a decrease in the risk of death was observed in men who received RT (AHR, 0.58; 95% CI, 0.40‐0.58 [P = .002]) or HT (AHR, 0.56; 95% CI, 0.37‐0.84 [P = .005]) after BCR.

CONCLUSIONS:

The occurrence of BCR was found to increase the risk of death in men undergoing RP for prostate cancer, and this risk appeared to increase as the time to BCR shortened. However, the addition of RT and/or HT in men with BCR significantly lowered this risk. Cancer 2010. © 2010 American Cancer Society.     

Immediate postmastectomy reconstruction is associated with improved breast cancer‐specific survival

BACKGROUND:

Although immediate breast reconstruction is increasingly offered as part of postmastectomy psychosocial rehabilitation, concerns remain that it may delay adjuvant therapy or impair detection of local recurrence. No single population‐based study has examined the relationship between immediate breast reconstruction and breast cancer‐specific survival.

METHODS:

By using data from the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registries, breast cancer‐specific survival was compared for female unilateral mastectomy patients who did or did not undergo immediate breast reconstruction. Cox proportional hazards models were fitted, adjusting for known demographic and disease severity variables and stratifying on reconstruction type (implant or autologous) and age.

RESULTS:

Improved breast cancer‐specific survival was observed among all immediate breast reconstruction patients compared with patients who underwent mastectomy alone (hazard ratio [HR] = 0.74; 95% confidence interval [CI], 0.68 to 0.80). Implant reconstruction patients below 50 years of age demonstrated the greatest apparent survival benefit (HR = 0.47; 95% CI 0.28 to 0.80). Similarly, autologous reconstruction was associated with improved cancer‐specific survival among patients below the age of 50 (HR = 0.58; 95% CI, 0.42 to 0.80) and between ages 50 to 69 (HR = 0.61; 95% CI, 0.43 to 0.85).

CONCLUSIONS:

Immediate breast reconstruction is associated with decreased breast cancer‐specific mortality, particularly among younger women. We believe this association is more likely attributable to imbalances in socioeconomic factors and access to care than to inadequate adjustment for tumor characteristics and disease severity. Further research is needed to identify additional prognostic factors responsible for the improved cancer survival among women undergoing immediate postmastectomy reconstruction. Cancer 2009. © 2009 American Cancer Society.     

Glutathione S-transferase gene polymorphisms and risk and survival of pancreatic cancer

BACKGROUND.

Pancreatic cancer is a multifactorial disease with metastasis‐prone and therapy‐resistant nature. The authors hypothesized that genetic variants of glutathione S‐transferase (GST) affect detoxification of carcinogens and anticancer agents in the human pancreas and, thus, the risk and survival of pancreatic cancer.

METHODS.

Genotypes of GSTM1, GSTT1, and GSTP1 were determined in 352 patients with pancreatic ductal adenocarcinoma and in a control group of 315 healthy, non‐Hispanic whites (frequency‐matched by age and sex). Survival analysis was performed in a subset of 290 patients. Epidemiological and clinical information was obtained. A multiple unconditional logistic regression model, a Cox proportional hazards model, and log‐rank tests were used for statistical analysis.

RESULTS.

No significant main effects of any of 3 GST genes on the risk of pancreatic cancer were observed. Subgroup analysis showed that older individuals (aged ≥62 years) who carried the GSTP1*C (¹⁰⁵Val‐¹¹⁴Val) containing genotype tended to have a reduced risk compared with younger individuals who carried the non‐*C genotype (for sex and pack‐years of smoking, the adjusted odd ratio was 0.54; 95% confidence interval [95% CI], 0.29–1.02). In a survival analysis of 138 patients who received 5‐flurorouracil, patients who carried the GSTP1*C containing genotype had a significantly longer survival than patients who carried the non‐*C genotype (multivariate hazard ratio, 0.45; 95% CI, 0.22–0.94).

CONCLUSIONS.

The GSTP1*C variant conferred a possible protective effect against pancreatic cancer in older individuals and a significant survival advantage in patients who received 5‐florouracil. The current findings must be confirmed before further inferences can be made. Cancer 2007 © 2007 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.     

The role of salvage surgery in patients with recurrent squamous cell carcinoma of the oropharynx

BACKGROUND:

The objective of this study was to comprehensively review overall survival, functional outcomes, and prognostic factors in patients who underwent salvage surgery for locally recurrent squamous cell carcinoma of the oropharynx (SCCOP) after initial radiotherapy.

METHODS:

The authors retrospectively reviewed 1681 consecutive patients who completed definitive therapy for primary SCCOP and identified 168 patients with locally recurrent SCCOP who underwent salvage surgery (41 patients), reirradiation or brachytherapy (18 patients), palliative chemotherapy (70 patients), or supportive care (39 patients).

RESULTS:

Twenty‐six of 39 patients (67%) developed a second recurrence after salvage surgery. The 3‐year overall survival rate for patients who underwent salvage surgery or received reirradiation, palliative chemotherapy, or supportive care were 48.7%, 31.6%, 3.7%, and 5.1%, respectively. For patients who underwent salvage surgery, older age (P = .03), the absence of a disease‐free interval (P < .01), and advanced recurrent tumor stage (P = .07) were associated with lower overall survival. Patients with recurrent neck disease (P = .01) and positive surgical margins (P = .04) had higher rates of recurrence after salvage surgery. Postoperative complications occurred in 19 patients (46%), and there were no perioperative deaths. Functionally, 71% of patients demonstrated ≥80% speech intelligibility, 68% were able to tolerate some oral intake, and 87% who required a tracheotomy subsequently were decannulated.

CONCLUSIONS:

Age, disease‐free interval, recurrent tumor stage, recurrent neck disease, and surgical margin status influenced overall survival or recurrence rate after salvage surgery for recurrent SCCOP. Although most patients had good functional outcomes, only a select group of patients with recurrent SCCOP achieved long‐term survival after salvage surgery. 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.     

Stathmin expression and its relationship to microtubule-associated protein tau and outcome in breast cancer

BACKGROUND:

Microtubule‐associated proteins (MAPs) endogenously regulate microtubule stability. Here, the prognostic value of stathmin, a destabilizing protein, was assessed in combination with MAP‐tau, a stabilizing protein, in order to evaluate microtubule stabilization as a potential biomarker.

METHODS:

Stathmin and MAP‐tau expression levels were measured in a breast cancer cohort (n = 651) using the tissue microarray format and quantitative immunofluorescence (AQUA) technology, then correlated with clinical and pathological characteristics and disease‐free survival.

RESULTS:

Univariate Cox proportional hazard models indicated that high stathmin expression predicts worse overall survival (hazard ratio [HR] = 1.48; 95% confidence interval [CI] = 1.119‐1.966; P = .0061). Survival analysis showed 10‐year survival of 53.1% for patients with high stathmin expression versus 67% for low expressers (log‐rank, P < .003). Cox multivariate analysis showed high stathmin expression was independent of age, menopausal status, nodal status, nuclear grade, tumor size, and estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression (HR = 1.19; 95% CI = 1.03‐1.37; P = .01). The ratio of MAP‐tau to stathmin expression showed a positive correlation to disease‐free survival (HR = 0.679; 95% CI = 0.517‐0.891; P = .0053) with a 10‐year survival of 65.4% for patients who had a high ratio of MAP‐tau to stathmin versus 52.5% 10‐year survival rate for those with a low ratio (log‐rank, P = .0009). Cox multivariate analysis showed the ratio of MAP‐tau to stathmin was an independent predictor of overall survival (HR = 0.609; 95% CI = 0.422‐0.879; P = .008).

CONCLUSIONS:

Low stathmin and high MAP‐tau are associated with increased microtubule stability and better prognosis in breast cancer. Cancer 2012. © 2012 American Cancer Society.     

Proton beam therapy for hepatocellular carcinoma

BACKGROUND:

The authors have published a series of studies evaluating the safety and efficacy of proton beam therapy for the treatment of hepatocellular carcinoma in a variety of clinical settings. In the current study, they retrospectively reviewed their entire experience treating hepatocellular carcinoma patients with proton beam therapy at their hospital‐based facility at the University of Tsukuba.

METHODS:

From November 2001 to December 2007, 333 patients with hepatocellular carcinoma were treated with proton beam therapy at the University of Tsukuba. A total of 318 patients were included in this study. Total dose delivered and fractionation scheme were determined by protocols that varied based on location of tumor. Survival rates and prognostic factors were assessed.

RESULTS:

Overall actuarial survival rates at 1‐year, 3‐years, and 5‐years were 89.5% (95% confidence interval [95% CI], 85.7‐93.1%), 64.7% (95% CI, 56.6‐72.9%), and 44.6% (95% CI, 29.7‐59.5%), respectively. Child‐Pugh liver function (hazards ratio [HR], 2.84; P < .01), T stage (HR, 1.94; P < .05), performance status (HR, 2.12; P < .01), and planning target volume (HR, 2.12; P < .05) significantly impacted survival. The 3‐year and 5‐year survival rates were 69.1% (95% CI, 59.9‐78.3%) and 55.9% (95% CI, 41.5‐70.3%), respectively, for patients with Child‐Pugh A disease and 51.9% (95% CI, 32.3‐71.5%) and 44.5% (95% CI, 23.1‐65.8%), respectively, for patients with Child‐Pugh B disease. The actuarial survival rates of patients with Child‐Pugh class A were statistically different between groups of planned target volume ≤125 mL and >125 mL (P < .05).

CONCLUSIONS:

The authors have shown proton beam therapy to be both safe and effective for the treatment of patients with hepatocellular carcinoma. They strongly recommend the consideration of proton beam therapy in patients for whom other treatment options are risky or contraindicated. Cancer 2009. © 2009 American Cancer Society.     

Cancer disparities in the context of Medicaid insurance: a comparison of survival for acute myeloid leukemia and Hodgkin's lymphoma by Medicaid enrollment

Background.

Because poverty is difficult to measure, its association with outcomes for serious illnesses such as hematologic cancers remains largely uncharacterized. Using Medicaid enrollment as a proxy for poverty, we aimed to assess potential disparities in survival after a diagnosis of acute myeloid leukemia (AML) or Hodgkin''s lymphoma (HL) in a nonelderly population.

Methods.

We used records from the New York (NY) and California (CA) state cancer registries linked to Medicaid enrollment records for these states to identify Medicaid enrolled and nonenrolled patients aged 21–64 years with incident diagnoses of AML or HL in 2002–2006. We compared overall survival for the two groups using Kaplan–Meier curves and Cox proportional hazards analyses adjusted for sociodemographic and clinical factors.

Results.

For HL, the adjusted risk for death for Medicaid enrolled compared with nonenrolled patients was 1.98 (95% confidence interval [CI], 1.47–2.68) in NY and 1.89 (95% CI, 1.43–2.49) in CA. In contrast, for AML, Medicaid enrollment had no effect on survival (adjusted hazard ratio, 1.00; 95% CI, 0.84–1.19 in NY and hazard ratio, 1.02; 95% CI, 0.89–1.16 in CA). These results persisted despite adjusting for race/ethnicity and other factors.

Conclusions.

Poverty does not affect survival for AML patients but does appear to be associated with survival for HL patients, who, in contrast to AML patients, require complex outpatient treatment. Challenges for the poor in adhering to treatment regimens for HL could explain this disparity and merit further study.     

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.     

Comparison of gefitinib versus erlotinib in patients with nonsmall cell lung cancer who failed previous chemotherapy

BACKGROUND:

Gefitinib and erlotinib are commonly used for salvage therapy in patients with nonsmall cell lung cancer (NSCLC) who have progressed on prior therapies. Although both agents have similar structure and have demonstrated efficacy in NSCLC, gefitinib and erlotinib have not been directly compared in terms of efficacy and other clinical outcomes in patients with NSCLC who have failed prior chemotherapy. This prompted us to analyze the clinical outcomes between gefitinib‐treated and erlotinib‐treated patients with metastatic or recurrent NSCLC.

METHODS:

A total of 467 patients with metastatic or recurrent NSCLC who had progressed on prior therapies and received gefitinib or erlotinib therapy between January 2006 and December 2008 were retrospectively reviewed. By using a matched‐pair case‐control study design, 171 pairs of gefitinib‐treated and erlotinib‐treated patients were matched according to sex, Eastern Cooperative Oncology Group (ECOG) performance status, histologic type, and smoking history.

RESULTS:

The median age of all patients was 58 years (range, 20‐85 years), and the median ECOG performance status was 1 (range, 0‐3). Of 342 patients, 294 (86%) received an epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitor as second‐line or third‐line therapy, whereas the remaining 14% had received >2 prior chemotherapy regimens before starting EGFR TK inhibitor therapy. The confirmed overall response rate was 35.1%, and the disease control rate was 64%. With 13.2 months of follow‐up, the median overall survival (OS) for the total 342 patients was 12.4 months (95% confidence interval [95% CI], 10.66‐14.14 months), and the median progression‐free survival (PFS) was 3.2 months (95% CI, 2.65‐3.75 months). The overall response rates and disease control rates in the gefitinib‐treated and erlotinib‐treated groups were 38% versus 32.2% (P = .273) and 63.2% versus 64.9%, respectively (P = .677). There was no statistically significant difference noted with regard to OS (median, 12.6 vs 12.1 months; P = 0.99) and PFS (median, 4.6 vs 2.7 months; P = .06) between the gefitinib‐treated and erlotinib‐treated groups.

CONCLUSIONS:

This retrospective analysis shows that gefitinib and erlotinib appear to have similar antitumor activity in terms of response rate and OS in pretreated patients with metastatic or recurrent NSCLC. Further prospective studies are warranted to elucidate any potential differences in toxicity and in dose intensity between gefitinib‐ and erlotinib‐treated patients. Cancer 2010. © 2010 American Cancer Society.     

Clinical benefits of systemic chemotherapy for patients with metastatic pheochromocytomas or sympathetic extra-adrenal paragangliomas: insights from the largest single-institutional experience

BACKGROUND:

The objective of this study was to evaluate the clinical benefits of systemic chemotherapy for patients with metastatic pheochromocytomas or sympathetic paragangliomas by assessing reductions in tumor size and blood pressure and improvements in overall survival (OS).

METHODS:

The authors retrospectively reviewed the medical records of patients with metastatic pheochromocytomas‐sympathetic paragangliomas who had received chemotherapy at The University of Texas MD Anderson Cancer Center.

RESULTS:

Clinical benefit and OS were assessed. Of 54 patients who received chemotherapy, 52 patients were evaluable for response. Seventeen patients (33%) experienced a response, which was defined as decreased or normalized blood pressure/decreased number and dosage of antihypertensive medications and/or reduced tumor size after the first chemotherapy regimen. The median OS was 6.4 years (95% confidence interval [CI], 5.2‐16.4 years) for responders and 3.7 years (95% CI, 3.0‐7.5 years) for nonresponders. Among the patients who had synchronous metastatic disease, a positive response at 1 year after the start of chemotherapy was associated with a trend toward longer OS (log‐rank test; P = .095). In a multivariate Cox proportional hazards model, the effect of response to chemotherapy on OS was significant (hazard ratio, 0.22; 95% CI, interval: 0.05‐1.0; P = .05). All responders had received dacarbazine and cyclophosphamide. Vincristine was included for 14 responders, and doxorubicin was included for 12 responders. The clinical factors that predicted response to chemotherapy could not be identified.

CONCLUSIONS:

The current results indicted that chemotherapy may decrease tumor size and facilitate blood pressure control in approximately 33% of patients with metastatic pheochromocytoma‐sympathetic paraganglioma. These patients exhibited longer survival. Cancer 2011. © 2011 American Cancer Society.     

Patterns and outcome of relapse after autologous stem cell transplantation for mantle cell lymphoma

BACKGROUND:

Autologous stem cell transplantation (autoSCT) has improved the outcome of patients with mantle cell lymphoma (MCL) considerably. However, little is known about the patterns and outcome of MCL recurrence after autoSCT.

METHODS:

The authors conducted a retrospective study of 118 patients with MCL who underwent autoSCT from August 1992 to August 2008 at 3 different referral centers in Germany.

RESULTS:

Fifty‐two relapses occurred for a cumulative incidence of 46% after 5 years. Only 3 patients relapsed after 5 years (at 90 months, 91 months, and 171 months) after undergoing autoSCT. A Cox regression analysis of the incidence of relapse identified not receiving rituximab before autoSCT and undergoing salvage autoSCT as predictive factors for relapse, whereas cytosine arabinoside intensification; a total body irradiation‐based, high‐dose regimen; patient age; and year of transplantation had no influence. The median overall survival (OS) after relapse was 23 months. Twenty patients (39%) underwent allogeneic stem cell transplantation (alloSCT) for relapse, and 11 of those patients remained in ongoing complete remission at the time of the current report. It is noteworthy that there were 4 long‐term survivors who lived for >5 years after relapse even without undergoing alloSCT. A Cox regression analysis of OS after relapse revealed that the response duration after autoSCT was an adverse predictor of OS, whereas alloSCT was associated with a significantly longer OS after relapse.

CONCLUSIONS:

The current results indicated that autoSCT was capable of inducing long‐term remission up to 16 years after treatment, but the outcome of patients with MCL who relapsed after autoSCT was poor, especially if their response duration after autoSCT was short. However, for a subset of patients with relapsed MCL, alloSCT may offer the possibility of durable survival, and individual patients can enjoy long‐term survival after relapse even without undergoing alloSCT. Cancer 2011. © 2010 American Cancer Society.     

Critical role of surgery in patients with gastroesophageal carcinoma with a poor prognosis after chemoradiation as defined by positron emission tomography

BACKGROUND:

The prognosis of patients with localized gastroesophageal carcinoma (LGC) can be defined after chemoradiation by the standardized uptake value (SUV) of positron emission tomography (PET). High SUV (HSUV) after chemoradiation portends a poor prognosis. The authors retrospectively examined the role of surgery in patients with HSUV after chemoradiation.

METHODS:

The authors analyzed the postchemoradiation PET scans of 204 LGC patients. One hundred twenty‐nine patients had HSUV. Two postchemoradiation variables were evaluated: SUV and surgery and their association with overall survival (OS) and event‐free survival (EFS). The log‐rank test, multivariate Cox proportional hazards model, and Kaplan‐Meier survival plots were used to assess the association between OS or EFS and the dichotomized SUV (using the median SUV as the cutoff) and surgery.

RESULTS:

The median SUV was 4.6. The OS of the 52 patients who had an SUV above the median and did not undergo surgery (HSUV‐NS) (median OS, 1.22 years; 95% confidence interval [95% CI], 1.02‐2.16 years) was much shorter than that of the 77 patients with an SUV above the median who underwent surgery (HSUV‐S) (median OS, 2.7 years; 95% CI, 2.43 years to not reached [P <.0001]). Similarly, the EFS for patients with HSUV‐NS was significantly shorter than that for patients with HSUV‐S (P = .001). In the multivariate analyses, patients who underwent surgery (irrespective of SUV) had a lower risk of death (P = .0001) and disease progression (P = .002).

CONCLUSIONS:

The data from the current study suggest that surgery may prolong OS and EFS in patients with a poor prognosis after chemoradiation as defined by PET. However, these data need confirmation. Cancer 2010. © 2010 American Cancer Society.     

Durable remission with salvage second autotransplants in patients with multiple myeloma

BACKGROUND:

High‐dose chemotherapy with autologous hematopoietic cell transplant (auto‐HCT) has been shown to improve survival in patients with newly diagnosed multiple myeloma. However, the role of salvage auto‐HCT for relapsed patients, particularly in the era of novel therapeutics, is not well defined.

METHODS:

The authors performed a retrospective analysis of all 44 myeloma patients (24 men, 20 women) who received a second auto‐HCT as salvage between January 3, 1992 and November 4, 2008 at The University of Texas MD Anderson Cancer Center.

RESULTS:

Median interval between the first and salvage auto‐HCT was 30 months (range, 2‐78 months). Median age at salvage HCT was 54 years (range, 38‐73 years), and median number of salvage treatment regimens was 2 (range, 0‐5). Eleven (25%) patients had high‐risk chromosomal abnormalities on conventional cytogenetic studies between diagnosis and salvage auto‐HCT. Ten patients (23%) experienced grade 3 or higher nonhematologic toxicity after the salvage auto‐HCT. One patient died within 100 days, for a treatment‐related mortality of 2%. Best responses after salvage chemotherapy + salvage auto‐HCT were as follows: complete response (CR) + near CR, 11%; partial response, 79%; overall response rate, 90%. Eighteen (41%) patients received post auto‐HCT maintenance therapy. Median follow‐up from salvage HCT was 41 months. Kaplan‐Meier estimates of median progression‐free survival (PFS) and overall survival (OS) from time of salvage auto‐HCT were 12.3 and 31.7 months, respectively. Median OS from the time of diagnosis was 75 months. In a fitted Bayesian multivariate model, shorter time to progression after first auto‐HCT, greater number of prior therapies, African American race, and immunoglobulin G subtype were significantly associated with worse OS.

CONCLUSIONS:

In selected myeloma patients, a second auto‐HCT for salvage therapy is well tolerated, with acceptable toxicity. The overall response rate and PFS are comparable to other salvage regimens. Cancer 2012;3549–3555. © 2011 American Cancer Society.     

Short- vs long-term androgen suppression plus external beam radiation therapy and survival in men of advanced age with node-negative high-risk adenocarcinoma of the prostate

BACKGROUND

The study evaluated whether the use of 3 years as compared with 6 months of androgen suppression therapy (AST) combined with external beam radiation therapy (RT) in the treatment of high‐risk prostate cancer was associated with prolonged survival in advanced age men.

METHODS

A pooled analysis of 311 men enrolled in 3 prospective randomized trials between 1987 and 2000 who received 6 months or 3 years of AST and RT for locally advanced or high‐grade localized adenocarcinoma of the prostate comprised the study cohort. Cox regression multivariable analysis was performed adjusting for known prognostic factors to determine whether the treatment received was associated with time to death after randomization. The median age and follow‐up was 70 and 5.9 years, respectively, during which 82 (26%) deaths occurred.

RESULTS

Treatment received was not significantly associated with survival time after randomization (adjusted hazard ratio [AHR]: 1.1; 95% confidence interval [CI]: 0.7, 1.8; P = .70), whereas age at randomization (AHR: 1.05; 95% CI: 1.01, 1.09; P = .02) was. The presence of Gleason score 8 to 10 cancers approached significance (AHR: 1.6; 95% CI: 0.9, 2.6; P = .09).

CONCLUSIONS

After adjusting for known prognostic factors, the treatment of node‐negative, high‐risk prostate cancer using 3 years as compared with 6 months of AST with RT was not associated with prolonged survival in men of advanced age. The European Organization for Research and Treatment of Cancer randomized trial will help answer whether unknown confounding factors affected the results of the study. Cancer 2007. © 2007 American Cancer Society.