Impact of comorbidity in elderly prostate cancer patients treated with brachytherapy

Objective

To analyze the correlations among comorbidity and overall survival (OS), biochemical progression-free survival (b-PFS) and toxicity in elderly patients with localized prostate cancer treated with ¹²⁵I brachytherapy.

Methods

Elderly men, aged ≥65 years, with low-intermediate risk prostate cancer, were treated with permanent ¹²⁵I brachytherapy as monotherapy. Comorbidity data were obtained from medical reports using age-adjusted Charlson comorbidity index (a-CCI). The patients were categorized into two age groups (<75 and ≥75 years old), and two comorbidity score groups (a-CCI ≤3 and >3). Toxicity was scored with Radiation Therapy Oncology Group (RTOG) scale.

Results

From June 2003 to October 2009, a total of 92 elderly patients underwent prostate brachytherapy, including 57 men (62%) with low-risk prostate cancer, and 35 men (38%) with intermediate-risk prostate cancer. The median age of patients was 75 years (range, 65-87 years). Forty-seven patients (51%) had a-CCI ≤3 and 45 patients (49%) a-CCI >3. With a median follow-up period of 56 months (range, 24-103 months), the 5-year actuarial OS and b-PFS were 91.3% and 92.4% respectively, without statistical significance between two Charlson score groups. Toxicity was mild. None of the patients experienced gastrointestinal (GI) toxicity, and only 4 patiens (4%) experienced late genitourinary (GU) grade-3 (G3) toxicity. No correlation between acute GU and GI toxicity and comorbidity was showed (P=0.50 and P=0.70, respectively).

Conclusions

Our data suggest that elderly men with low-intermediate risk prostate cancer and comorbidity can be considered for a radical treatment as ¹²⁵I low-dose rate brachytherapy.Key Words: Prostate cancer, brachytherapy, elderly, comorbidity, toxicity, overall survival, biochemical control     

Phase I/II clinical trial of dendritic-cell based immunotherapy (DCVAC/PCa) combined with chemotherapy in patients with metastatic,castration-resistant prostate cancer

Purpose

We conducted an open-label, single-arm Phase I/II clinical trial in metastatic CRPC (mCRPC) patients eligible for docetaxel combined with treatment with autologous mature dendritic cells (DCs) pulsed with killed LNCaP prostate cancer cells (DCVAC/PCa). The primary and secondary endpoints were safety and immune responses, respectively. Overall survival (OS), followed as a part of the safety evaluation, was compared to the predicted OS according to the Halabi and MSKCC nomograms.

Experimental design

Twenty-five patients with progressive mCRPC were enrolled. Treatment comprised of initial 7 days administration of metronomic cyclophosphamide 50 mg p.o. DCVAC/PCa treatment consisted of a median twelve doses of 1 × 10⁷ dendritic cells per dose injected s.c. (Aldara creme was applied at the site of injection) during a one-year period. The initial 2 doses of DCVAC/PCa were administered at a 2-week interval, followed by the administration of docetaxel (75 mg/m2) and prednisone (5 mg twice daily) given every 3 weeks until toxicity or intolerance was observed. The DCVAC/PCa was then injected every 6 weeks up to the maximum number of doses manufactured from one leukapheresis.

Results

No serious DCVAC/PCa-related adverse events have been reported. The median OS was 19 months, whereas the predicted median OS was 11.8 months with the Halabi nomogram and 13 months with the MSKCC nomogram. Kaplan-Meier analyses showed that patients had a lower risk of death compared with both MSKCC (Hazard Ratio 0.26, 95% CI: 0.13–0.51) and Halabi (Hazard Ratio 0.33, 95% CI: 0.17–0.63) predictions. We observed a significant decrease in Tregs in the peripheral blood. The long-term administration of DCVAC/PCa led to the induction and maintenance of PSA specific T cells. We did not identify any immunological parameter that significantly correlated with better OS.

Conclusions

In patients with mCRPC, the combined chemoimmunotherapy with DCVAC/PCa and docetaxel was safe and resulted in longer than expected survival. Concomitant chemotherapy did not preclude the induction of specific anti-tumor cytotoxic T cells.     

The impact of diabetes mellitus on prognosis of early breast cancer in Asia

Background.

Diabetes mellitus (DM) has been implicated in influencing the survival duration of patients with breast cancer. However, less is known about the impact of DM and other comorbidities on the breast cancer–specific survival (BCS) and overall survival (OS) outcomes of Asian patients with early-stage breast cancer.

Patients and Methods.

The characteristics of female patients with newly diagnosed, early-stage breast cancer were collected from the Taiwan Cancer Registry database for 2003–2004. DM status and other comorbidities were retrieved from Taiwan''s National Health Insurance database. The BCS and OS times of patients according to DM status were estimated via the Kaplan–Meier method. Cox''s proportional hazard model was used to estimate adjusted hazard ratios (HRs) for the effects of DM, comorbidities, and other risk factors on mortality.

Results.

In total, 4,390 patients were identified and 341 (7.7%) presented with DM. The 5-year BCS and OS rates were significantly greater in DM patients than in non-DM patients (BCS, 85% versus 91%; OS, 79% versus 90%). Furthermore, after adjusting for clinicopathologic variables and comorbidities, DM remained an independent predictor of shorter BCS (adjusted HR, 1.53) and OS (adjusted HR, 1.71) times. Subgroup analyses also demonstrated a consistent prognostic influence of DM across different groups.

Conclusion.

In Asian patients with early-stage breast cancer, DM is an independent predictor of lower BCS and OS rates, even after adjusting for other comorbidities. The integration of DM care as part of the continuum of care for early-stage breast cancer should be emphasized.     

Impact of comorbidity on tolerability and survival following curative intent intensity modulated radiotherapy in older patients with nasopharyngeal cancer

Objective

This study aimed to evaluate the predictive factors for survival and acute toxicities in older patients with NPC treated with curative intent IMRT.

Diabetes mellitus is associated with increased mortality in patients receiving curative therapy for hepatocellular carcinoma

Background.

Diabetes mellitus (DM) is closely associated with hepatocarcinogenesis. This study explores the prognostic impact of DM in patients who received curative therapy for localized hepatocellular carcinoma (HCC).

Methods.

Patients who had been diagnosed with stage I or II HCC in 2003 and 2004 and received surgical resection or local ablation therapy were identified from the population-based Taiwan National Cancer Registry. Data pertaining to DM and other comorbidities were retrieved from the Taiwan National Health Insurance database. Liver cancer-specific survival (LCS), liver disease-related survival (LDS) and overall survival (OS) rates were compared between patients with and without DM. The presence of other comorbidities and tumor status were adjusted using multivariate analysis.

Results.

A total of 931 patients who fulfilled the study criteria were analyzed; 185 (20%) of them had DM (type 1 or type 2). The LCS, LDS, and OS rates were significantly worse for patients with DM than patients without DM (all p < .001). After adjusting for age, sex, tumor stage, treatment, and the presence of other comorbidities, DM remained an independent predictor of poorer LCS (hazard ratio [HR] = 1.57; p < .001), LDS (HR = 1.70; p < .001), and OS (HR = 1.69; p < .001). The associations between DM and mortality were consistent among subgroups, irrespective of tumor size, stage, treatment modality, and liver cirrhosis.

Conclusions.

DM is an independent factor for poorer prognosis in patients who received curative therapy for localized HCC.     

Comparative Effectiveness of Mitoxantrone Plus Prednisone Versus Prednisone Alone in Metastatic Castrate‐Resistant Prostate Cancer After Docetaxel Failure

Background.

Mitoxantrone was approved for use in metastatic castrate-resistant prostate cancer (mCRPC) based on pain palliation without observed survival benefit in a small phase III trial in 1996. To re-evaluate for possible survival benefits in a larger contemporary sample and to demonstrate analytic uses of the newly available Project Data Sphere online resource, we used data from control arms of completed clinical trials to compare survival and toxicity among patients with postdocetaxel mCRPC treated with mitoxantrone and prednisone.

Patients and Methods.

Control arm data from two phase III randomized control trials, SUN 1120 and TROPIC, were used to examine the efficacy of mitoxantrone plus prednisone (n = 305) versus prednisone alone (n = 257) among patients with postdocetaxel mCRPC. Propensity score matching was used to balance patient characteristics between the separate trials, conditioned on age and key prognostic variables of survival. The primary outcome was overall survival. Secondary endpoints evaluated safety.

Results.

Median survival was similar among patients receiving mitoxantrone plus prednisone versus prednisone alone (385 days vs. 336 days; deceleration factor = 0.04; 95% confidence interval: −0.12 to 0.22). Prevalence of several any-grade toxicity, including fatigue, back pain, and peripheral neuropathy, was increased among patients who received mitoxantrone.

Conclusion.

There was no significant survival benefit for mitoxantrone plus prednisone over prednisone alone among men with mCRPC after docetaxel therapy. This finding is consistent with prior studies showing no survival advantage with mitoxantrone in the predocetaxel setting. Furthermore, our data suggest that mitoxantrone may be associated with increased toxicity compared with prednisone alone.     

Effect of response quality and line of treatment with rituximab on overall and disease-free survival of patients with B-cell lymphoma

Background

The introduction of rituximab into the treatment of patients with non-Hodgkin’s lymphomas has improved the overall response rate, as well as the response duration and the overall survival of patients with B-cell lymphomas. But only a few studies have addressed the question whether the better response (complete response) and the early introduction of rituximab into the treatment translate into the better survival. The aim of this retrospective study was to assess the potential relationship between either the quality of the response or the line of the rituximab treatment and the overall survival (OS) as well as the disease-free survival (DFS) of patients with B-cell lymphomas.

Patients and methods.

In the study, we analysed treatment outcomes in patients with different histological types of B-cell lymphomas who were treated at the Institute of Oncology between 2003 and 2007 with rituximab and chemotherapy. We included only patients who had the level of CD20 expression assessed prior to the introduction of the treatment with quantitative flow-cytometric measurements. The OS and DFS were evaluated by Kaplan-Meier survival curves.

Results

One hundred and fourteen patients were enrolled in the study. Patients who achieved a complete response after the rituximab containing treatment had a significantly longer OS than those reaching a partial response (hazard ratio [HR], 0.34; 95% CI, 0.05 to 0.91, P = 0.0375) and than patients with stable (hazard ratio [HR], 0.11; 95% CI, 0.0002 to 0.033, P < 0.0001) or progressive disease (hazard ratio [HR], 0.09; 95% CI, 0.003 to 0.03, P < 0.0001). Patients who achieved a complete response (CR; n = 70; 61.4%) had also a significantly longer DFS (hazard ratio [HR], 0.26; 95% CI, 0.021 to 0.538, P = 0.0068) than those reaching only a partial response (PR; n = 17; 14.9%). Patients treated with rituximab as the first-line treatment (n = 50; 43.9%) had a significantly longer OS than those treated with rituximab for the first (hazard ratio [HR], 0.27; 95% CI, 0.106 to 0.645, P = 0.0036) or second relapse (hazard ratio [HR], 0.22; 95% CI, 0.078 to 0.5, P = 0.0006). Also the DFS of patients treated with rituximab as the first-line treatment (n = 46; 52.9%) was significantly longer (hazard ratio [HR], 0.32; 95% CI, 0.088 to 0.9, P = 0.0325) than in patients treated with rituximab for their first relapse (n = 25; 28.7%).

Conclusions

These data indicate that a better response to rituximab therapy presumably translates into an improved OS and DFS for patients with B-cell lymphomas. The early introduction of rituximab into the treatment (i.e. first-line treatment) might improve OS. Therefore, the response adapted first-line therapy with rituximab should be considered when the treatment decision is taken in B-cell lymphoma patients.     

Chemotherapy-Induced Neutropenia and Outcome in Patients With Metastatic Castration-Resistant Prostate Cancer Treated With First-Line Docetaxel

Background

Neutropenia is a common side effect associated with docetaxel use. We retrospectively investigated the association between chemotherapy-induced neutropenia and survival in metastatic castration-resistant prostate cancer (mCRPC) patients receiving first-line docetaxel.

The Prognostic Impact of Type 2 Diabetes Mellitus on Early Cervical Cancer in Asia

Background.

Many studies have shown that type 2 diabetes mellitus (DM) increases the risk for several types of cancer but not cervical cancer (CC). Although DM and insulin-like growth factor 1 have preclinical and clinical implications for CC, less is known about the prognostic impact of DM on patients with early stage CC.

Patients and Methods.

We used the nationwide Taiwan Cancer Registry database to collect the characteristics of stage I–IIA cervical cancer patients diagnosed between 2004 and 2008. DM and other comorbidities were retrieved from the National Health Insurance database. Cervical cancer-specific survival (CSS) and overall survival (OS) times of patients according to DM status were estimated using the Kaplan-Meier method. We used a Cox proportional hazards model to calculate adjusted hazard ratios (HRs) for the effects of DM and other risk factors on mortality.

Results.

A total of 2,946 patients had primary stage I–IIA CC and received curative treatments, and 284 (9.6%) had DM. The 5-year CSS and OS rates for patients with DM were significantly lower than those without DM (CSS: 85.4% vs. 91.5%; OS: 73.9% vs. 87.9%). After adjusting for clinicopathologic variables and comorbidities, DM remained an independent unfavorable prognostic factor for CSS (adjusted HR: 1.46) and OS (adjusted HR: 1.55).

Conclusion.

In Asian patients with early cervical cancer, DM is an independent unfavorable prognostic factor influencing both OS and CSS, even after curative treatments.

Implications for Practice:

Type 2 diabetes mellitus (DM) increases the incidence of several types of cancer but not cervical cancer (CC); however, less is known about the impact of DM on patients who already have CC. This study suggests that DM may increase the risk of cancer recurrence and death for early stage CC patients, even after curative treatments. Incorporating DM control should be considered part of the continuum of care for early stage CC patients, and close surveillance during routine follow-up in this population is recommended.     

Prognostic factors in elderly patients with malignant pleural mesothelioma: results of a multicenter survey

Background:

The incidence of malignant pleural mesothelioma (MPM) in elderly patients is increasing. There are no specific guidelines for their management.

Methods:

The clinical records of elderly patients (⩾70 years old) with MPM referred from January 2005 to November 2011 to six Italian Centres were reviewed. Age, gender, histology, International Mesothelioma Interest Group (IMIG) stage, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), Charlson Comorbidity Index (CCI) and treatment modalities were analysed and correlated to overall survival (OS).

Results:

In total, 241 patients were identified. Charlson Comorbidity Index was ⩾1 in 92 patients (38%). Treatment was multimodality therapy including surgery in 18, chemotherapy alone in 180 (75%) and best supportive care in 43 cases (18%). Chemotherapy was mainly pemetrexed based. Median OS was 11.4 months. Non-epithelioid histology (HR 2.32; 95% CI 1.66–3.23, P<0.001), age ⩾75 years (HR 1.44; 95% CI 1.08–1.93, P=0.014), advanced (III–IV) stage (HR 1.47; 95% CI 1.09–1.98, P=0.011) and CCI⩾1 (HR 1.38; 95% CI 1.02–1.85, P=0.034) were associated to a shorter OS. Treatment with pemetrexed was associated with improved OS (HR 0.40; 95% CI 0.28–0.56, P<0.001).

Conclusions:

Non-epithelioid histology, age ⩾75 years, advanced IMIG stage and presence of comorbidities according to CCI were significant prognostic factors in elderly patients with MPM. Treatment with pemetrexed-based chemotherapy was feasible in this setting. Prospective dedicated trials in MPM elderly patients selected according to prognostic factors including comorbidity scales are warranted.     

Treatment Outcome of Breast Cancer with Pathologically Proven Synchronous Ipsilateral Supraclavicular Lymph Node Metastases

Purpose

The aim of this study was to investigate the prognosis, patterns of failure, and prognostic factors for breast cancer patients with pathologically proven synchronous ipsilateral supraclavicular lymph node (ISCLN) metastases.

Methods

We reviewed the records of breast cancer patients with pathologically proven ISCLN metastases. Local aggressive treatment was defined as treatment including surgery, axillary lymph node dissection (ALND), ISCLN excision, radiotherapy (RT), and chemotherapy.

Results

A total of 111 patients were included. The 5-year overall survival (OS) and disease-free survival (DFS) rates were 64.2% and 56.2%, respectively. On univariate analysis, RT, ALND, trastuzumab treatment, hormone receptor (HR) status, and local aggressive treatment were identified as significant factors for OS. The 5-year OS for 73 patients who received local aggressive treatment was superior to that of 38 patients who received nonaggressive treatment (70.9% vs. 49.3%, p=0.036). Multivariate analysis showed that RT, HR status, and trastuzumab were significant variables for the 5-year OS and DFS.

Conclusion

Multimodality treatment with surgery, taxane-based chemotherapy, hormone therapy, and RT is strongly recommended for breast cancer patients with synchronous ISCLN metastases.     

Pretreatment Neutrophil‐to‐Lymphocyte Ratio in Metastatic Castration‐Resistant Prostate Cancer Patients Treated With Ketoconazole: Association with Outcome and Predictive Nomogram

Background.

The neutrophil-to-lymphocyte ratio (NLR), an inflammation marker, is prognostic in several cancers. We assessed the association between the pretreatment NLR and outcome of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with the CYP17 inhibitor ketoconazole.

Methods.

This was an international, retrospective study of 156 mCRPC patients treated with ketoconazole. The independent effect of the pretreatment NLR and factors associated with treatment outcome were determined by multivariate analysis.

Results.

Seventy-eight patients (50%) had a ≥50% decline in prostate-specific antigen (PSA). The median progression-free survival (PFS) time was 8 months. Excluded from the analysis were 23 patients without available data on their NLR and those with a recent health event or treatment associated with a blood count change. Sixty-two patients (47%) had a pretreatment NLR >3. Risk factors associated with the PFS outcome were a pretreatment NLR >3 and PSA doubling time (PSADT) <3 months and a prior response to a gonadotropin-releasing hormone agonist of <24 months or to an antiandrogen of <6 months. The number of risk factors was used to form a predictive nomogram by patient categorization into favorable (zero or one factor), intermediate (two factors), and poor (three or four factors) risk groups.

Conclusions.

In mCRPC patients treated with ketoconazole, the pretreatment NLR and PSADT, and prior response to androgen-deprivation therapy, may be associated with the PFS time and used to form a risk stratification predictive nomogram.     

Prognostic and predictive value of plasma testosterone levels in patients receiving first-line chemotherapy for metastatic castrate-resistant prostate cancer

Background:

Biomarkers for metastatic castration-resistant prostatic cancer (mCRPC) are an unmet medical need.

Methods:

The prognostic and predictive value for survival and response to salvage hormonal therapy (SHT) of baseline testosterone level (TL) was analysed in a cohort of 101 mCRPC patients participating in 9 non-hormonal first-line chemotherapy phase II–III trials. Inclusion criteria in all trials required a TL of <50 ng dl⁻¹.

Results:

Median age: 70 years; visceral metastases: 19.8% median prostate-specific antigen (PSA): 50.7 ng ml⁻¹; median TL: 11.5 ng dl⁻¹. Median overall survival (OS; 24.5 months) was significantly longer if baseline TL was above (High TL; n=52) than under (Low TL; n=49) the TL median value (32.7 vs 22.4 months, respectively; P=0.0162, hazard ratio (HR)=0.6). The presence of anaemia was an unfavourable prognostic factor (median OS: 20.6 vs 28.4 months; P=0.0025, HR=1.88 (CI95%: 1.01–3.48)). Patients presenting both anaemia and low testosterone had a worse outcome compared to those with one or none of them (median OS: 17.9 vs 22.4 vs 38.1 months; P=0.0024). High vs Low TL was associated with PSA response rate (55.6% vs 21.7%) in 41 patients receiving SHT.

Conclusion:

Testosterone level under castration range was a prognostic factor for survival mCRPC patients. The PSA response to SHT differed depending on TLs. Testosterone levels might help in treatment decision.     

Comparative effectiveness study of breast-conserving surgery and mastectomy in the general population: A NCDB analysis

Purpose

Recent studies have revealed that breast-conserving surgery (BCS) with radiotherapy (RT) led to better survival than mastectomy in some populations. We compared the efficacy of BCS+RT and mastectomy using the National Cancer Database (NCDB, USA).

Methods

Non-metastatic breast cancers in the NCDB from 2004–2011 were identified. The Kaplan-Meier method, Coxregression and propensity score analysis were used to compare the overall survival (OS) among patients with BCS+RT, mastectomy alone and mastectomy+RT.

Results

A total of 160,880 patients with a median follow-up of 43.4 months were included. The respective 8-year OS values were 86.5%, 72.3% and 70.4% in the BCS+RT, mastectomy alone and mastectomy+RT group, respectively (P < 0.001). After exclusion of patients with comorbidities, mastectomy (alone or with RT) remained associated with a lower OS in N0 and N1 patients. However, the OS of mastectomy+RT was equivalent to BCS+RT in N2–3 patients. Among patients aged 50 or younger, the OS benefit of BCS+RT over mastectomy alone was statistically significant (HR1.42, 95% CI 1.16–1.74), but not clinically significant (<5%) in N0 patients, whereas in N2–3 patients, the OS of BCS+RT was equivalent to mastectomy+RT (85.2% vs. 84.8%). The results of the propensity analysis were similar.

Conclusions

BCS+RT resulted in improved OS compared with mastectomy ± RT in N0 and N1 patients. In N2–3 patients, BCS+RT has an OS similar to mastectomy+RT when patients with comorbidities were excluded. Among patients aged 50 or younger, the OS of BCS+RT is equivalent to mastectomy ± RT.     

Longer waiting times for early stage cervical cancer patients undergoing radical hysterectomy are associated with diminished long-term overall survival

Objective

The aim of this study was to evaluate the impact of surgical waiting time on clinical outcome in early stage cervical cancer.

Methods

The cohort consisted of 441 patients diagnosed with stages IA2-IB1cervical cancer who underwent radical hysterectomy and pelvic node dissection. The patients were divided into two groups based on surgical waiting time. The associations between waiting time and other potential prognostic factors with clinical outcome were evaluated.

Results

The median surgical waiting time was 43 days. Deep stromal invasion (hazard ratio [HR], 2.5; 95% confidence interval [CI], 1.4 to 4.6; p=0.003) and lymph node metastasis (HR, 2.9; 95% CI, 1.3 to 6.7; p=0.026) were identified as independent prognostic factors for recurrence-free survival while no prognostic significance of surgical waiting time was found (p=0.677). On multivariate analysis of overall survival (OS), only deep stromal invasion (HR, 2.6; 95% CI, 1.3 to 5.0; p=0.009) and lymph node metastasis (HR, 3.6; 95% CI, 1.5 to 8.6; p=0.009) were identified as independent prognostic factors for OS. Although OS showed no significant difference between short (≤8 weeks) and long (>8 weeks) waiting times, multivariate analysis of OS with time-varying effects revealed that a waiting time longer than 8 weeks was associated with poorer long-term survival (after 5 years; HR, 3.4; 95% CI, 1.3 to 9.2; p=0.021).

Conclusion

A longer surgical waiting time was associated with diminished long-term OS of early stage cervical cancer patients.     

Pro-angiogenic cytokines for prediction of outcomes in patients with advanced hepatocellular carcinoma

Background:

We previously reported that expressions of the pro-angiogenic cytokines angiopoietin-2 (Ang-2), follistatin, granulocyte colony-stimulating factor, hepatocyte growth factor, leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, and vascular endothelial growth factor were associated with the response to sorafenib in patients with advanced hepatocellular carcinoma (HCC). The aim of the present study is to examine the same relationship in a larger cohort.

Methods:

In the current retrospective cohort study, we measured serum levels of the eightcytokines in 120 consecutive HCC patients who were treated with sorafenib. We evaluated the effects of increased expression of serum cytokines on progression-free survival (PFS) and overall survival (OS).

Results:

Elevated expression of Ang-2 correlated both with significantly shorter PFS (hazard ratio (HR), 1.84; 95% confidence interval (CI), 1.21–2.81), and OS (HR, 1.95; 95% CI, 1.21–3.17). Patients with more than three cytokines expressed above the median similarly had significantly shorter PFS (HR, 1.98; 95% CI, 1.30–3.06) and OS (HR, 1.94; 95% CI, 1.19–3.22). Differences in OS were evident in cases with the evidence of macroscopic vascular invasion or extrahepatic metastasis.

Conclusion:

High expression of Ang-2 or more than cytokines in serum is associated with poor PFS and OS in HCC patients treated with sorafenib.     

What Do Prostate Cancer Patients Die Of?

Background.

A recent rise in the incidence of prostate cancer and a more favorable outcome have increased the proportions of other causes of death in affected men. Extending the survival of prostate cancer patients thus requires knowledge of all causes of death.

Methods.

Data on the population, cancers, and causes of death were gathered from the nationwide Swedish Family-Cancer Database. A Cox regression model, comparing prostate cancer patients with all other men, was applied. Hazard ratios (HR) were calculated both for the underlying cause and for dying with a specific cause listed among multiple causes of death.

Findings.

Among 686,500 observed deaths, 62,500 were prostate cancer patients. For underlying causes other than prostate cancer, the highest cause-specific HRs were found for external causes (HR, 1.24; 95% confidence interval [CI], 1.16–1.31), diseases of the pulmonary circulation (HR, 1.22; 95% CI, 1.09–1.37), and heart failure (HR, 1.18; 95% CI, 1.11–1.24). For specific multiple causes, the highest HRs were found for anemia (HR, 2.28; 95% CI, 2.14–2.42), diseases of the pulmonary circulation (HR, 1.61; 95% CI, 1.55–1.68), and urinary system disease (HR, 1.90; 95% CI, 1.84–1.96).

Interpretations.

Prostate cancer patients have a higher risk for dying from various causes other than prostate cancer, including external causes and heart failure. Mechanisms have been proposed linking these elevated risks to both cancer and treatment. More attention should be paid to comorbidities in men with prostate cancer. The present study fulfills a gap in the knowledge of death causes in prostate cancer patients.     

First‐Line Treatment Patterns and Clinical Outcomes in Patients With HER2‐Positive and Hormone Receptor‐Positive Metastatic Breast Cancer From registHER

Background.

Limited data are available describing the natural history of patients with HER2-positive and hormone receptor (HR)-positive metastatic breast cancer (MBC). We examined first-line treatment patterns and clinical outcomes in patients with HER2-positive, HR-positive MBC in a real-world setting.

Methods.

registHER is a prospective, observational cohort of 1,023 patients with HER2-positive MBC diagnosed within 6 months of enrollment and followed until death, disenrollment, or June 2009 (median follow-up time: 27 months). Demographics, first-line treatment patterns, and clinical outcomes were examined for 530 HER2-positive, HR-positive patients. Progression-free survival (PFS) and overall survival (OS) times were examined. Multivariate analyses adjusted for baseline demographic and prognostic factors.

Results.

HER2-positive, HR-positive patients receiving first-line trastuzumab plus hormonal therapy had significantly longer PFS times than patients who received hormonal therapy only (13.8 vs. 4.8 months; adjusted hazard ratio [HR]: 0.37, 95% confidence interval [CI]: 0.22–0.60); a nonsignificant reduction in OS time was observed (adjusted HR: 0.55, 95% CI: 0.27–1.14). Compared with patients who received first-line trastuzumab plus chemotherapy, patients who received first-line trastuzumab plus chemotherapy and hormonal therapy had longer median PFS times (20.4 months vs. 9.5 months; adjusted HR: 0.53, 95% CI: 0.42–0.68); a statistically significant reduction in risk of death was observed (adjusted HR: 0.50, 95% CI: 0.36–0.70). Sequential use of chemotherapy and hormonal therapy was associated with improved OS times when compared with concurrent use (adjusted PFS HR: 0.81, 95% CI: 0.54–1.21; adjusted OS HR: 0.48, 95% CI: 0.26–0.89).

Conclusions.

These real-world data in patients with HER2-positive/HR-positive MBC provide evidence that, with or without chemotherapy, dual targeting of HRs and HER2 receptors is associated with significantly prolonged PFS and OS times.     

VeriStrat? has prognostic value in advanced stage NSCLC patients treated with erlotinib and sorafenib

Background:

The serum proteomic test VeriStrat has been shown to be able to classify advanced non-small cell lung cancer (NSCLC) patients for overall survival (OS) after treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). In this study, VeriStrat was evaluated as a pre-treatment stratification tool in patients with advanced stage NSCLC for treatment with the combination of erlotinib and sorafenib, considering both OS and progression-free survival (PFS) as end points.

Methods:

Serum samples from 50 patients treated within the context of a phase II trial of first-line erlotinib and sorafenib were analysed with VeriStrat, a fully locked mass spectrometry-based test that identifies patients likely to have good or poor outcome on EGFR therapy based on eight distinct features in mass spectra. Analysis was performed fully blinded to all clinical data, and then the outcome data were analysed with respect to the obtained serum classifications.

Results:

VeriStrat classified pre-treatment samples into two groups, VeriStrat Good and VeriStrat Poor, which were significantly different in OS (hazard ratio (HR) 0.30, log-rank P=0.009) and in PFS (HR 0.40, log-rank P=0.035).

Conclusion:

VeriStrat has shown its potential for stratification of unselected, advanced stage NSCLC patients treated in first line with a combination of erlotinib and sorafenib.     

Results of the FLAC European Database of Metastatic Castration-Resistant Prostate Cancer Patients Treated With Docetaxel,Cabazitaxel, and Androgen Receptor–Targeted Agents

Background

Several agents have demonstrated an overall survival (OS) benefit in patients with metastatic castration-resistant prostate cancer (mCRPC); however, the optimal sequencing of these therapies is unknown as a result of a lack of prospective randomized controlled trials. This retrospective study aimed to identify clinical factors influencing outcomes and to determine optimal treatment sequencing in patients with mCRPC treated with cabazitaxel (CABA) and/or androgen receptor–targeted agents (ART) after androgen-deprivation therapy (ADT) and docetaxel (DOC).