Clinical Predictors of Survival for Patients with Stage IV Cancer Referred to Radiation Oncology

BackgroundThere is an urgent need for a robust, clinically useful predictive model for survival in a heterogeneous group of patients with metastatic cancer referred to radiation oncology.MethodsFrom May 2012 to August 2013, 143 consecutive patients with stage IV cancer were prospectively evaluated by a single radiation oncologist. We retrospectively analyzed the effect of 29 patient, laboratory and tumor-related prognostic factors on overall survival using univariate analysis. Variables that were statistically significant on univariate analysis were entered into a multivariable Cox regression to identify independent predictors of overall survival.ResultsThe median overall survival was 5.5 months. Four prognostic factors significantly predicted survival on multivariable analysis including ECOG performance status (0–1 vs. 2 vs. 3–4), number of active tumors (1 to 5 vs. ≥6), albumin levels (≥3.4 vs. 2.4 to 3.3 vs. <2.4 and primary tumor site (Breast, Kidney or Prostate vs. Other). Risk group stratification was performed by assigning points for adverse prognostic factors resulting in very low, low, intermediate and high risk groups. The median survival was >31.4 months for very low risk patients compared to 14.5 months for low risk, 4.1 months for intermediate risk and 1.2 months for high risk (p<0.001).ConclusionsThese data suggest that a model that considers performance status, extent of disease, primary tumor site and serum albumin represents a simple model to accurately predict survival for patients with stage IV cancer who are potential candidates for radiation therapy.     

调强放射治疗在宫颈癌治疗中的临床研究

目的:探讨中晚期宫颈癌患者应用调强放射治疗(IMRT)技术在提高靶区剂量与减少正常组织受量方面的价值.方法:40例中晚期宫颈癌患者均给予全程IMRT 1.8～2.2 Gy/次,每周4次外照射和1次内照射,外照射的处方剂量为50～55 Gy,中位剂量为53.5 Gy,内照射共给6次,每次5 Gy.同时拟设计该40例患者2野和4野的放疗计划,拟给予相同的处方剂量,比较危险器官(OAR)直肠、小肠、膀胱和骨髓的受照射剂量和体积.结果:40例患者均完成全程的IMRT,放射治疗计划靶区(PTV)的平均剂量为54.5 Gy,90%的等剂量曲线(中位剂量53.5 Gy)可以覆盖99%以上的肉眼靶区(GTV)体积.IMRT与普通2野和4野放疗组比较,小肠、直肠、膀胱和骨髓的受照射剂量和体积均明显减少(P<0.05).急慢性放射反应明显减轻.1,2年生存率比较,差异无统计学意义.结论:IMRT放疗技术可以使患者的放疗靶区获得较为理想的剂量分布,邻近危险器官得到很好的保护,从而减小了急慢性放疗反应,毒副反应可以耐受,但未能提高近期生存率.     

Clinicopathologic Predictors of Survival in Patients with Desmoplastic Melanoma

Background and Objectives

Desmoplastic melanoma is a unique subtype of melanoma which typically affects older patients who often have comorbidities that can adversely affect survival. We sought to identify melanoma-specific factors influencing survival in patients with desmoplastic melanoma.

Methods

Retrospective review from 1993 to 2011 identified 316 patients with primary desmoplastic melanoma. Clinicopathologic characteristics were correlated with nodal status and outcome.

Results

Fifty-five patients (17.4%) had nodal disease: 33 had a positive sentinel lymph node biopsy and 22 developed nodal recurrences (no sentinel lymph node biopsy or false-negative sentinel lymph node biopsy). Nodal disease occurred more often in younger patients and in cases with mixed compared with pure histology (26.7% vs. 14.6%); both of these variables significantly predicted nodal status on multivariable analysis (p<0.05). After a median follow-up of 5.3 years, recurrence developed in 87 patients (27.5%), and 111 deaths occurred. The cause of death was known in 79 cases, with 47 deaths (59.5%) being melanoma-related. On multivariable analysis, Breslow thickness, mitotic rate ≥1/mm² and nodal status significantly predicted melanoma-specific survival (p<0.05).

Conclusions

Nodal status predicts melanoma-specific survival in patients with desmoplastic melanoma. However, since patients with desmoplastic melanoma represent an older population, and a considerable proportion of deaths are not melanoma-related (40.5%), comorbidities should be carefully considered in making staging and treatment decisions in this population.     

Clinical Significance of IGFBP-3 Methylation in Patients with Early Stage Gastric Cancer

BACKGROUND: IGFBP-3 is a multifunctional protein that inhibits growth and induces apoptosis of cancer cells. Hypermethylation of the promoter represses expression of the IGFBP-3 gene. We undertook this study to assess the impact of IGFBP-3 methylation on survival of early stage gastric cancer patients. METHODS: Of the 482 tissue samples from gastric cancer patients who underwent curative surgery, IGFBP-3 methylation was tested in 138 patients with stage IB/II gastric cancer. We also analyzed IGFBP-3 methylation in 26 gastric cancer cell lines. IGFBP-3 methylation was evaluated by methylation-specific polymerase chain reaction (MethyLight). Statistical analyses, all two-sided, were performed to investigate the prognostic effects of methylation status of the IGFBP-3 promoter on various clinical parameters. RESULTS: Hypermethylation of IGFBP-3 was observed in 26 (19%) of the 138 stage IB/II gastric cancer patients. Clinicopathological factors such as age, Lauren classification, sex, tumor infiltration, lymph node metastasis, and histologic grade did not show a statistically significant association with the methylation status of the IGFBP-3 promoter. Patients with a hypermethylated IGFBP-3 promoter had similar 8-year disease-free survival compared with those without a hypermethylated IGFBP-3 promoter (73% vs 75%, P = .78). In subgroup analyses, females, but not males, seemed to have poorer prognosis for DFS and OS in the subset of patients with IGFBP-3 methylation as compared with those without IGFBP-3 methylation (8-year DFS: 55.6% vs 71.6%, P = .3694 and 8-year overall survival: 55.6% vs 68.4%, P = .491, respectively) even with no statistical significance. CONCLUSIONS: The status of IGFBP-3 methylation as measured by methylation-specific polymerase chain reaction proposed the modest role for predicting survival in specific subgroups of patients with early-stage gastric cancer who undergo curative surgery. However, this needs further investigation.     

Predictors for Half-Year Outcome of Impairment in Daily Life for Back Pain Patients Referred for Physiotherapy: A Prospective Observational Study

Background and Objective

From observational studies, there is only sparse information available on the predictors of development of impairment in daily life for patients receiving physiotherapy. Therefore, our aim was to identify factors which predict impairment in daily life for patients with back pain 6 months after receiving physiotherapy.

Methods

We conducted a prospective cohort study with 6-month follow-up. Patients were enrolled for treatment in private physiotherapy practices. Patients with a first physiotherapy referral because of thoracic or low back pain, aged 18 to 65 years were included. Primary outcome impairment was measured utilising the 16-item version of the Musculoskeletal Function Assessment Questionnaire. Therapy was documented on a standardized form. Baseline scores for impairment in daily life, symptom characteristics, sociodemographic and psychosocial factors, physical activity, nicotine consumption, intake of analgesics, comorbidity and delivered primary therapy approach were investigated as possible predictors. Univariate and multiple linear regression analyses were performed.

Results

A total of 792 patients participated in the study (59% female, mean age 44.4 (SD 11.4), with 6-month follow-up results available from 391 patients. In univariate analysis 17 variables reached significance. In multiple linear regression identified predictors were: impairment in daily life before therapy, mental disorders, duration of the complaints, self-prognosis on work ability, rheumatoid arthritis, age, form of stress at work and physical activity. The variables explain 34% of variance (adjusted R², p<0.001).

Conclusions

With minimal information available from observational studies on the predictors of development of back problems for physiotherapy patients, this study adds new knowledge for forming appropriate referral guidelines. Impairment in daily life before therapy, mental disorder as comorbidity and the duration of the complaints can be named as outstanding factors. The results of this study can be used to facilitate comparison of patient therapy goals with the prognosis in everyday practice.     

Serum Biomarkers Associated with Clinical Outcomes Fail to Predict Brain Metastases in Patients with Stage IV Non-Small Cell Lung Cancers

BackgroundLung cancers account for the majority of brain metastases which pose major therapeutic challenges. Biomarkers prognosticating for the development of brain metastases in patients with non-small cell lung cancers (NSCLC) may improve personalized care. Six serum proteomic biomarkers were previously investigated at Memorial Sloan Kettering but their associations with brain metastases were unknown.MethodsSerum NSE, CYFRA 21–1, ProGRP, SCC-Ag, TIMP1, and HE4 by ELISA-based proteomic assays were prospectively collected from consecutive patients with stage IV NSCLC. Pre-treatment serum biomarker levels as well as age, histology, and epidermal growth factor receptor (EGFR) mutation status were evaluated for association with the baseline presence of brain metastases using logistic regression and multivariable analysis. For patients without brain metastases at baseline, the cumulative incidence of subsequent brain metastases were compared according to baseline biomarkers and clinical factors using Gray’s test.ResultsA total of 118 patients were enrolled, 31 (26%; 95% CI 0.19–0.35) had brain metastases at baseline and a further 26 (22%; 95% CI 0.15–0.30) developed brain metastases subsequently. Pre-treatment serum biomarker levels were available in 104 patients. There was no significant association between the six serum biomarkers and the baseline presence or subsequent development of brain metastases. Age younger than 65 years was the only clinical factor significantly associated with brain metastasis at baseline (OR 3.00; 95% CI 1.22–7.34, P = 0.02) by multivariable analysis. A trend toward increased cumulative incidence of subsequent brain metastases was observed in patients with EGFR mutation (p = 0.2), but this was not statistically significant possibly due to small sample size.ConclusionsSerum NSE, CYFRA 21–1, Pro-GRP, SCC-Ag, TIMP1, and HE4 are not significantly associated with brain metastases. Our methods taking into account follow-up time may be applied to independent datasets to identify a patient cohort with a higher biologic propensity for developing brain metastases. Such information may be useful for the study of agents targeting the development of brain metastases.     

Survival of Patients with Oral Cavity Cancer in Germany

The purpose of the present study was to describe the survival of patients diagnosed with oral cavity cancer in Germany. The analyses relied on data from eleven population-based cancer registries in Germany covering a population of 33 million inhabitants. Patients with a diagnosis of oral cavity cancer (ICD-10: C00-06) between 1997 and 2006 are included. Period analysis for 2002–2006 was applied to estimate five-year age-standardized relative survival, taking into account patients'' sex as well as grade and tumor stage. Overall five-year relative survival for oral cavity cancer patients was 54.6%. According to tumor localization, five-year survival was 86.5% for lip cancer, 48.1% for tongue cancer and 51.7% for other regions of the oral cavity. Differences in survival were identified with respect to age, sex, tumor grade and stage. The present study is the first to provide a comprehensive overview on survival of oral cavity cancer patients in Germany.     

Molecular Predictors of Long-Term Survival in Glioblastoma Multiforme Patients

Glioblastoma multiforme (GBM) is the most common and aggressive adult primary brain cancer, with <10% of patients surviving for more than 3 years. Demographic and clinical factors (e.g. age) and individual molecular biomarkers have been associated with prolonged survival in GBM patients. However, comprehensive systems-level analyses of molecular profiles associated with long-term survival (LTS) in GBM patients are still lacking. We present an integrative study of molecular data and clinical variables in these long-term survivors (LTSs, patients surviving >3 years) to identify biomarkers associated with prolonged survival, and to assess the possible similarity of molecular characteristics between LGG and LTS GBM. We analyzed the relationship between multivariable molecular data and LTS in GBM patients from the Cancer Genome Atlas (TCGA), including germline and somatic point mutation, gene expression, DNA methylation, copy number variation (CNV) and microRNA (miRNA) expression using logistic regression models. The molecular relationship between GBM LTS and LGG tumors was examined through cluster analysis. We identified 13, 94, 43, 29, and 1 significant predictors of LTS using Lasso logistic regression from the somatic point mutation, gene expression, DNA methylation, CNV, and miRNA expression data sets, respectively. Individually, DNA methylation provided the best prediction performance (AUC = 0.84). Combining multiple classes of molecular data into joint regression models did not improve prediction accuracy, but did identify additional genes that were not significantly predictive in individual models. PCA and clustering analyses showed that GBM LTS typically had gene expression profiles similar to non-LTS GBM. Furthermore, cluster analysis did not identify a close affinity between LTS GBM and LGG, nor did we find a significant association between LTS and secondary GBM. The absence of unique LTS profiles and the lack of similarity between LTS GBM and LGG, indicates that there are multiple genetic and epigenetic pathways to LTS in GBM patients.     

The Association between Pre-Treatment Serum 25-Hydroxyvitamin D and Survival in Newly Diagnosed Stage IV Prostate Cancer

Background/Aims

Emerging evidence in the literature suggests a positive association between serum 25-hydroxyvitamin D [25(OH)D], a standard indicator of vitamin D status, and survival in certain types of cancer. We investigated this relationship in newly diagnosed stage IV prostate cancer patients.

Methods

A consecutive cohort of 125 newly diagnosed stage IV prostate cancer patients underwent a baseline serum 25(OH)D evaluation prior to receiving any treatment at our institution between January 2008 and December 2011. We used the vitamin D categories of “deficient (<20 ng/ml)”, “insufficient (20 to 32 ng/ml)”, and “sufficient (>32 ng/ml)”. Cox regression was used to evaluate the prognostic significance of serum 25(OH)D after adjusting for relevant confounders.

Results

Mean age at diagnosis was 60 years. Of the 125 patients, 32 (25.6%) were deficient, 49 (39.2%) were insufficient and 44 (35.2%) were sufficient in vitamin D at the time of diagnosis. The median survival in deficient, insufficient and sufficient cohorts was 47.8, 44.0 and 52.6 months respectively (p = 0.60). On univariate analysis, four variables demonstrated a statistically significant association with survival: nutritional status, bone metastasis, corrected serum calcium and serum albumin (p<0.05 for all). On multivariate analysis, five variables demonstrated statistically significant associations with survival: hospital location, age, bone metastasis, serum albumin and corrected serum calcium (p<0.05 for all). Serum vitamin D status was not significant on either univariate or multivariate analysis.

Conclusion

Contrary to previously published research, we found no significant association between pre-treatment serum 25(OH)D and survival in newly diagnosed stage IV prostate cancer patients. The lack of a significant association between serum vitamin D and survival in our study could perhaps be due to the fact that the disease was far too advanced in our patients for vitamin D levels to have any impact on prognosis.     

Long-Term Survival in a Large Cohort of Patients with Venous Thrombosis: Incidence and Predictors

Background

Venous thrombosis is a common disease with a high mortality rate shortly after the event. However, details on long-term mortality in these patients are lacking. The aim of this study was to determine long-term mortality in a large cohort of patients with venous thrombosis.

Methods and Findings

4,947 patients from the Multiple Environmental and Genetic Assessment study of risk factors for venous thrombosis (MEGA study) with a first nonfatal venous thrombosis or pulmonary embolism and 6,154 control individuals without venous thrombosis, aged 18 to 70 years, were followed up for 8 years. Death and causes of death were retrieved from the Dutch death registration. Standardized mortality ratios (SMRs) were calculated for patients compared with control individuals. Several subgroups were studied as well.736 participants (601 patients and 135 controls) died over a follow-up of 54,948 person-years. The overall mortality rate was 22.7 per 1,000 person-years (95% CI 21.0–24.6) for patients and 4.7 per 1,000 person-years (95% CI 4.0–5.6) for controls. Patients with venous thrombosis had a 4.0-fold (95% CI 3.7–4.3) increased risk of death compared with controls. The risk remained increased up to 8 years after the thrombotic event, even when no additional comorbidities were present. The highest risk of death was found for patients with additional malignancies (SMR 5.5, 95% CI 5.0–6.1). Main causes of death were diseases of the circulatory system, venous thrombosis, and malignancies. Main limitation was a maximum age of 70 at time of inclusion for the first event. Therefore results can not be generalized to those in the highest age categories.

Conclusions

Patients who experienced a first venous thrombosis had an increased risk of death which lasted up to 8 years after the event, even when no comorbidities were present at time of thrombosis. Future long-term clinical follow-up could be beneficial in these patients. Please see later in the article for the Editors'' Summary     

Simultaneous Integrated Boost Radiotherapy in Unresectable Stage IV (M0) Head and Neck Squamous Cell Cancer Patients: Daily Clinical Practice

AimTo evaluate clinical outcome in locally-advanced stage IV (M0) head and neck cancer patients treated using intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) in daily clinical practice.BackgroundDespite SIB-IMRT has been reported as a feasible and effective advanced head and neck cancer treatment, there are few data about its concurrent use with systemic therapies.Material and MethodsWe reviewed 41 staged IV (M0) head and neck cancer patients treated in two radiotherapy units in the city of Messina (Italy) during the last six years, using intensity modulated techniques-SIB. 22/41 patients had concomitant chemotherapy or cetuximab. Acute and late toxicities, objective response (OR) rate, local control (LC) and overall survival (OS) have been evaluated.Results37/41 patients received the planned doses of radiotherapy, 2 patients died during the therapy. The major acute regional toxicities were skin reaction and mucositis. A case of mandibular osteoradionecrosis was recorded. At completion of treatment, OR was evaluated in 38 patients: 32/38 patients (84.2%) had complete (55.3%) and partial (28.9%) response. The 1- and 5-year LC rates were 73.4% and 69.73%, respectively. The 1-, 3-, and 5-year OS rates were 85.93%, 51.49% and 44.14%, respectively. No statistically significant differences in outcomes have been observed in patients treated with radiotherapy alone vs. irradiation concomitant to chemo/biotherapy. The median OS was 45 months.ConclusionSIB-IMRT is safeand can be used with concomitant chemotherapy/biotherapy in real-life daily clinical practice. SIB-IMRT alone is a valid alternative in patients unfit for systemic therapies.     

Cancer with Diabetes: Prevalence,Metabolic Control,and Survival in an Academic Oncology Practice

ObjectiveTo determine the prevalence of diabetes mellitus, glycemic control, and impact of diabetes on over all survival in an academic oncology practice.MethodsData on cancer patients (1999 to 2008) were retrieved from the institutional cancer registry and linked to electronic files to obtain diabetes status and hemoglobin A1c (A1C) values within the first 6 months of cancer diagnosis. Overall survival by cancer type with and without diabetes was compared using Cox regression.ResultsExcluding skin and hematologic malignancies, 15,951 cancer cases were identified. Overall diabe tes prevalence was 6.8% (n = 1,090), declining over time (P < 0.001). Diabetes was common among patients with pancreatic (9.8% [61 of 624]), colorectal (7.7% [89 of 1,151]), or bladder cancers (7.6% [68 of 899]). Patients with diabetes were older (mean age, 70 versus 66 years; P < 0.001) and more likely to be male (66.3% [723 of 1,090] versus 60.2% [8,949 of 14,858]; P < 0.001). The mean A1C among diabetic cancer patients was 6.8% and did not dif fer across cancer types (P = 0.80). Only 58.6% (331 of 565) of diabetic cancer patients had all A1C < 7.0% during the first 6 months following cancer diagnosis. Pancreatic cancer patients with coexisting diabetes had better overall survival than pancreatic cancer patients without diabetes (hazard ratio, 0.60; 95% confidence interval 0.44 to 0.80; P < 0.001). Conversely, diabetic prostate cancer patients had worse overall survival than prostate cancer patients without diabetes (hazard ratio, 1.36; 95% confidence interval 1.05 to 1.76; P = 0.02).ConclusionIn this academic oncology practice, diabetes was common, glycemic control often was subopti mal, and survival varied by cancer type. Additional study is needed to optimize glucose management and investigate mechanisms underlying age, sex, and survival differences. (Endocr Pract. 2012;18:898-905)