Factors influencing health-related quality of life among Korean cancer survivors

Abstract

Objective

Early cancer detection and remarkable improvements in cancer treatment have seen the cancer survival rate grow steadily for the past 40 years. Despite expectations regarding treatment effectiveness, acceptable quality of life, and a comfortable death, patients with cancer generally have a decreased quality of life. The study aim was to examine the factors influencing health-related quality of life among South Korean cancer survivors for future development of an intervention to enhance their survivorship.

Methods

Korea National Health and Nutrition Examination Survey 2008–2012 data regarding 1020 cancer survivors were used for analysis. Health-related quality of life was measured using the EuroQol 5-Dimension.

Results

The factors influencing health-related quality of life were age, educational status, employment status, income, smoking, time since diagnosis, subjective health status, stress, depression, and suicidal ideation.

Conclusions

Individual-centered clinical interventions that consider dimensional-influencing factors, including subjective health status, are needed to improve cancer survivors' health-related quality of life. Subsequent systematic studies are needed regarding dimension-specific differences according to cancer types and time since diagnosis. Copyright © 2016 John Wiley & Sons, Ltd.

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PR55{alpha} subunit of protein phosphatase 2A supports the tumorigenic and metastatic potential of pancreatic cancer cells by sustaining hyperactive oncogenic signaling

The protein phosphatase 2 (PP2A) holoenzyme consists of a catalytic subunit, a scaffold subunit, and a regulatory subunit. Based on loss of function analysis using PP2A catalytic inhibitors or inhibition via tumor viral antigens, limited studies suggest that PP2A is a putative tumor suppressor. However, PP2A has also been shown to facilitate the activation of oncogenic signaling pathways when associated with specific regulatory subunits. In this study, we investigated the possible oncogenic role of PP2A in pancreatic cancer. We found a striking increase in the expression of PR55α (PPP2R2A), a PP2A regulatory subunit, in pancreatic cancer cells compared to normal pancreatic epithelial cells. Consistently, PR55α expression was markedly elevated in pancreatic ductal adenocarcinoma tissues compared to adjacent normal pancreatic tissues (P<0.0001) and correlated with poor survival of pancreatic cancer patients (P<0.0003). RNAi-mediated depletion of PR55α in pancreatic cancer cell lines resulted in diminished phosphorylation of both AKT and ERK1/2 (MAPK3/1) and decreased protein levels of β-catenin (CTNNB1). Accordingly, pancreatic cancer cells with reduced PR55α expression exhibited significantly impaired properties of transformation, including attenuated cell growth, clonogenicity, mobility, and anchorage-independent growth. Moreover, orthotopic implantation of PR55α-depleted pancreatic cancer cells into nude mice resulted in markedly reduced tumorigenicity (P<0.001) and distant metastases. Together, these results suggest that PR55α promotes pancreatic cancer development by sustaining hyperactivity of multiple oncogenic signaling pathways, including AKT, ERK, and Wnt. These studies also provide a basis for exploring PR55α as a diagnostic or therapeutic target in pancreatic cancer.

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Drosophila Brat and human ortholog TRIM3 maintain stem cell equilibrium and suppress brain tumorigenesis by attenuating Notch nuclear transport

Cancer stem cells exert enormous influence on neoplastic behavior, in part by governing asymmetric cell division and the balance between self-renewal and multipotent differentiation. Growth is favored by deregulated stem cell division, which enhances the self-renewing population and diminishes the differentiation program. Mutation of a single gene in Drosophila, Brain Tumor (Brat), leads to disrupted asymmetric cell division resulting in dramatic neoplastic proliferation of neuroblasts and massive larval brain overgrowth. To uncover mechanisms relevant to deregulated cell division in human glioma stem cells, we first developed a novel adult Drosophila brain tumor model using brat-RNAi driven by the neuroblast specific promoter inscuteable. Suppressing Brat in this population led to accumulation of actively proliferating neuroblasts and a lethal brain tumor phenotype. brat-RNAi caused upregulation of Notch signaling, a node critical for self-renewal, by increasing protein expression and enhancing nuclear transport of NICD. In human glioblastoma, we demonstrated that the human ortholog of Drosophila Brat, TRIM3, similarly suppressed NOTCH1 signaling and markedly attenuated the stem cell component. We also found that TRIM3 suppressed nuclear transport of active NOTCH1 (NICD) in glioblastoma, and demonstrated that these effects are mediated by direct binding of TRIM3 to the Importin complex. Together, our results support a novel role for Brat/TRIM3 in maintaining stem cell equilibrium and suppressing tumor growth by regulating NICD nuclear transport.

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In vivo visualization and characterization of epithelial-mesenchymal transition in breast tumors

The activation of the epithelial-to-mesenchymal transition (EMT) program is a critical step in cancer progression and metastasis, but visualization of this process at the single cell level, especially in vivo, remains challenging. We established an in vivo approach to track the fate of tumor cells based on a novel EMT-driven fluorescent color switching breast cancer mouse model and intravital two-photon laser scanning microscopy. Specifically, the MMTV-PyMT, Rosa26-RFP-GFP, and Fsp1-Cre triple transgenic mouse model was used to monitor the conversion of RFP-positive epithelial cells to GFP-positive mesenchymal cells in mammary tumors under the control of the Fsp1 (ATL1) promoter, a gate-keeper of EMT initiation. RFP-positive cells were isolated from the tumors, sorted, and transplanted into mammary fat pads of SCID mice to monitor EMT during breast tumor formation. We found that the conversion from RFP to GFP-positive and spindle-shaped cells was a gradual process, and that GFP-positive cells preferentially localized close to blood vessels, independent of tumor size. Furthermore, cells undergoing EMT expressed high levels of the HGF receptor, c-Met, and treatment of RFP-positive cells with the c-Met inhibitor, cabozantinib, suppressed the RFP-to-GFP conversion in vitro. Moreover, administration of cabozantinib to mice with palpable RFP-positive tumors resulted in a silent EMT phenotype whereby GFP-positive cells exhibited reduced motility, leading to suppressed tumor growth. In conclusion, our imaging technique provides a novel opportunity for visualizing tumor EMT at the single cell level and may help to reveal the intricacies underlying tumor dynamics and treatment responses.

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Activation of the MDA5-IPS1 viral sensing pathway induces cancer cell death and type I interferon-dependent antitumor immunity

Melanoma differentiation-associated gene 5 (MDA-5, IFIH1), a cytosolic innate pattern recognition receptor, functions as a first line of defense against viral infection by sensing double-stranded RNA (dsRNA). Ectopic expression of MDA-5 has been shown to induce cancer cell death, but the mechanism of action by which MDA-5 exerts these cytotoxic effects is unclear. Here, we demonstrate that ectopic expression of MDA-5 via replication incompetent adenovirus (Ad.Mda-5) initiates multiple signaling cascades, culminating in cytotoxicity and type I interferon (IFN) production in mouse and human prostate cancer cells. This intrinsic dual activity of MDA-5 required the adaptor protein IFN-β promoter stimulator 1 (IPS-1, MAV) and could be functionally uncoupled. MDA-5 lacking N-terminal caspase-recruitment domains (CARDs) engaged an intracellular death program in cancer cells, but was unable to efficiently stimulate expression of IFN-β. In contrast to cancer cells susceptible to MDA-5-mediated cytotoxicity, normal cells were highly resistant and instead developed a robust type I IFN response. Strikingly, intratumoral delivery of Ad.Mda-5 led to regression of pre-established prostate cancers and development of long-lasting antitumor immune memory, which was primarily attributed to the activation of tumor-reactive cytotoxic T lymphocytes and/or natural killer cells. Using the CARDs-truncated MDA-5 mutant, silencing of IPS-1, and antibody blockade of the IFN-α/β-receptor, we further demonstrate that type I IFN signaling was crucial for in situ MDA-5-induced protective antitumor immunity. Therefore, deliberately targeting the evolutionarily conserved MDA-5-IPS-1 antiviral pathway in tumors can provoke parallel tumoricidal and immunostimulatory effects that bridge innate and adaptive immune responses for the therapeutic treatment of cancer.

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Inflammation-dependent IL-18 signaling restricts hepatocellular carcinoma growth by enhancing the accumulation and activity of tumor-infiltrating lymphocytes

Chronic inflammation in liver tissue is an underlying cause of hepatocellular carcinoma (HCC). High levels of inflammatory cytokine interleukin IL-18 in the circulation of patients with HCC correlates with poor prognosis. However, conflicting results have been reported for IL-18 in HCC development and progression. In this study, we used tissue specimens from HCC patients and clinically relevant mouse models of HCC to evaluate IL-18 expression and function. In a mouse model of liver fibrosis that recapitulates a tumor-promoting microenvironment, global deletion of the IL-18 receptor IL18R1 enhanced tumor growth and burden. Similarly, in a carcinogen-induced model of liver tumorigenesis, IL18R1 deletion increased tumor burden. Mechanistically, we found that IL-18 exerted inflammation-dependent tumor-suppressive effects largely by promoting the differentiation, activity and survival of tumor-infiltrating T cells. Finally, differences in the expression of IL-18 in tumor tissue versus non-tumor tissue was more predictive of patient outcome than overall tissue expression. Taken together, our findings resolve a long-standing contradiction regarding a tumor-suppressive role for IL-18 in established HCC and provide a mechanistic explanation for the complex relationship between its expression pattern and HCC prognosis.

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Retroileal colorectal anastomosis after extended left colectomy: application for laparoscopic surgery

Abstract

Tension-free anastomosis is often difficult to achieve after extended left hemicolectomy because the residual colon is too short to reach the rectal stump. Retroileal colorectal anastomosis is very simple and useful for obtaining tension-free anastomosis. We first applied this technique to laparoscopic operations. We herein describe the procedure of laparoscopic retroileal colorectal anastomosis.

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Surgical and non-surgical management of repeat pulmonary metastasis from sarcoma following first pulmonary metastasectomy

Abstract

Purpose

Although repeat pulmonary metastasectomy for sarcoma is not uncommon and associated with a favorable survival in select patients, there is a paucity of data on the demographics and tumor characteristics of patients with repeat pulmonary metastasis following complete resection of pulmonary metastases from osteogenic or soft tissue sarcoma.

Methods

A retrospective chart review was performed to identify patients with isolated repeat pulmonary metastasis after complete resection of pulmonary metastases from sarcoma at Kyoto University Hospital between January 1990 and December 2014. Isolated pulmonary metastasis was defined as limited to presumable pulmonary metastasis according to the follow-up radiologic workup.

Results

Thirty-five patients were identified to have repeat pulmonary metastasis. Thirty patients underwent attempted repeat pulmonary metastasectomy (including 21 undergoing documented complete resection and 7 undergoing documented incomplete or aborted resections). Five patients received non-surgical management. The median follow-up period was 16 months (range 1–234) from repeat pulmonary metastasis. The five-year overall survival of the whole patient cohort and those undergoing repeat pulmonary metastasectomy were 37.6 and 41.1 %, respectively, from repeat pulmonary metastasis.

Conclusions

A majority of patients with repeat pulmonary metastasis from sarcoma undergo repeat metastasectomy, which is associated with favorable survival outcomes. However, a greater accumulation of data on non-surgically managed patients is needed as such information is currently limited available.

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Cancer's Moonshot

Journal of Adolescent and Young Adult Oncology Mar 2016, Vol. 5, No. 1: 1-1.


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Clinical characteristics associated with non-small-cell lung cancer harboring ALK rearrangements in Chinese patients

Future Oncology Ahead of Print.


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Systemic therapies in the treatment of non-small-cell lung cancer brain metastases

Future Oncology Ahead of Print.


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Incorporating genetic counseling into clinical care for children and adolescents with cancer

Future Oncology Ahead of Print.


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Metformin with everolimus and octreotide in pancreatic neuroendocrine tumor patients with diabetes

Future Oncology Ahead of Print.


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Comparison of ILK and ERP29 expressions in benign and malignant pancreatic lesions and their clinicopathological significances in pancreatic ductal adenocarcinomas

Abstract

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor of the pancreas with poor prognosis. The lack of understanding of the molecular mechanisms of PDAC and biomarkers for early diagnosis might be two of the reasons for the poor prognosis of PDAC.

Materials and methods

ILK and ERP29 protein expressions in PDAC, peritumoral tissues, benign pancreatic lesions, and normal pancreatic tissues were measured by immunohistochemistry and the clinical and pathological significances of ILK and ERP29 in PDAC were analyzed.

Results

The percentages of positive ILK and negative ERP29 expressions were significantly higher in PDAC tumors than in peritumoral tissues, benign pancreatic tissues, and normal pancreatic tissues (P < 0.01). Benign pancreatic lesions with positive ILK and negative ERP29 expressions exhibited dysplasia or intraepithelial neoplasia. The percentage of cases with positive ILK and negative ERP29 expressions was significantly lower in PDAC patients without lymph node metastasis and invasion, and having TNM stage I/II disease than in patients with lymph node metastasis, invasion, and TNM stage III/IV disease (P < 0.05 or P < 0.01). Kaplan–Meier survival analysis showed that positive ILK and negative ERP29 expressions were significantly associated with survival in PDAC patients (P < 0.001). Cox multivariate analysis revealed that positive ILK and negative ERP29 expressions were independent poor prognosis factors in PDAC patients.

Conclusions

Positive ILK and negative ERP29 expressions are associated with the progression of PDAC and poor prognosis in patients with PDAC.

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Targeted next-generation sequencing of locally advanced squamous cell carcinomas of the head and neck reveals druggable targets for improving adjuvant chemoradiation

Publication date: April 2016
Source:European Journal of Cancer, Volume 57
Author(s): I. Tinhofer, V. Budach, M. Saki, R. Konschak, F. Niehr, K. Jöhrens, W. Weichert, A. Linge, F. Lohaus, M. Krause, K. Neumann, V. Endris, A. Sak, M. Stuschke, P. Balermpas, C. Rödel, M. Avlar, A.L. Grosu, A. Abdollahi, J. Debus, C. Belka, S. Pigorsch, S.E. Combs, D. Mönnich, D. Zips, M. Baumann
BackgroundDespite clear differences in clinical presentation and outcome, squamous cell carcinomas of the head and neck (SCCHN) arising from human papilloma virus (HPV) infection or heavy tobacco/alcohol consumption are treated equally. Next-generation sequencing is expected to reveal novel targets for more individualised treatment.Patients and methodsTumour specimens from 208 patients with locally advanced squamous cell carcinoma of the hypopharynx, oropharynx or oral cavity, all uniformly treated with adjuvant cisplatin-based chemoradiation, were included. A customised panel covering 211 exons from 45 genes frequently altered in SCCHN was used for detection of non-synonymous point and frameshift mutations. Mutations were correlated with HPV status and treatment outcome.ResultsMutational profiles and HPV status were successfully established for 179 cases. HPV– tumours showed an increased frequency of alterations in tumour suppressor genes compared to HPV+ cases (TP53 67% versus 4%, CDKN2A 18% versus 0%). Conversely, HPV+ carcinomas were enriched for activating mutations in driver genes compared to HPV– cases (PIK3CA 30% versus 12%, KRAS 6% versus 1%, and NRAS 4% versus 0%). Hotspot TP53 missense mutations in HPV– carcinomas correlated with an increased risk of locoregional recurrence (hazard ratio [HR] 4.3, 95% confidence interval [CI] 1.5–12.1, P=0.006) and death (HR 2.2, 95% CI 1.1–4.4, P=0.021). In HPV+ SCCHN, driver gene mutations were associated per trend with a higher risk of death (HR 3.9, 95% CI 0.7–21.1, P=0.11).ConclusionsDistinct mutation profiles in HPV– and HPV+ SCCHN identify subgroups with poor outcome after adjuvant chemoradiation. Mutant p53 and the phosphoinositide 3-kinase pathway were identified as potential druggable targets for subgroup-specific treatment optimisation.



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Vaccination using melanoma cells treated with p19arf and interferon beta gene transfer in a mouse model: a novel combination for cancer immunotherapy

Abstract

Previously, we combined p19^Arf (Cdkn2a, tumor suppressor protein) and interferon beta (IFN-β, immunomodulatory cytokine) gene transfer in order to enhance cell death in a murine model of melanoma. Here, we present evidence of the immune response induced when B16 cells succumbing to death due to treatment with p19^Arf and IFN-β are applied in vaccine models. Use of dying cells for prophylactic vaccination was investigated, identifying conditions for tumor-free survival. After combined p19^Arf and IFN-β treatment, we observed immune rejection at the vaccine site in immune competent and nude mice with normal NK activity, but not in NOD-SCID and dexamethasone immunosuppressed mice (NK deficient). Combined treatment induced IL-15, ULBP1, FAS/APO1 and KILLER/DR5 expression, providing a mechanism for NK activation. Prophylactic vaccination protected against tumor challenge, where markedly delayed progression and leukocyte infiltration were observed. Analysis of primed lymphocytes revealed secretion of TH1-related cytokines and depletion protocols showed that both CD4⁺ and CD8⁺ T lymphocytes are necessary for immune protection. However, application of this prophylactic vaccine where cells were treated either with IFN-β alone or combined with p19^Arf conferred similar immune protection and cytokine activation, yet only the combination was associated with increased overall survival. In a therapeutic vaccine protocol, only the combination was associated with reduced tumor progression. Our results indicate that by harnessing cell death in an immunogenic context, our p19^Arf and IFN-β combination offers a clear advantage when both genes are included in the vaccine and warrants further development as a novel immunotherapy for melanoma.

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Erratum

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Phase II study of bevacizumab plus irinotecan on the treatment of relapsed resistant small cell lung cancer

Abstract

Purpose

This phase II study investigates the efficacy and safety of DNA topoisomerase I inhibitor irinotecan plus bevacizumab a monoclonal antibody against VEGF (BEVIRI) in patients with relapsed chemo-resistant SCLC.

Methods

Patients who previously completed treatment with cisplatin–etoposide who relapsed within 3 months, had measurable extensive-stage SCLC, ECOG performance status 0–2 and adequate hematologic, renal and hepatic function, were given intravenous irinotecan 175 mg/m² plus intravenous bevacizumab 7.5 mg/kg on day 1 and 15 in 30 day cycles for a target of at least four cycles. No patients had received prophylactic intracranial irradiation. Treatment response was assessed with computer tomography scans with the completion of two consecutive cycles. Primary endpoint was overall response rate (ORR).

Results

Thirty-two patients were enrolled and 28 of them were eligible for evaluation of response, toxicity and survival. The median age was 63.5 years (range 48–73). The ORR (CR and PR) was 25 % (95 % CI 8.9–41.0) and including patients with stable disease overall disease control rate at 2 months was 89 % (95 % CI 77.41–100). The median duration of response was 6 months, median progression-free survival was 3 months (mean PFS: 3.2, 95 % CI 2.7–3.7), and median overall survival was 6 months (mean OS: 6.3, 95 % CI 5.4–7.1). The PFS rate at 6 months was 3.6 %, and 1-year OS rate was 3.6 %. The median number of cycles received was 4.5 (range 1–6). There were two (7.1 %) hematologic (neutropenia) and one (3.5 %) non-hematologic (proteinuria) serious grades 3–4 adverse reactions without necessitating treatment discontinuation.

Conclusion

BEVIRI combination in relapsed chemo-resistant SCLC patients demonstrates promising efficacy and low toxicity compared to historical controls. Further investigation is warranted.

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Use of claims data to estimate annual cervical cancer screening percentages in Portland metropolitan area, Oregon

Publication date: April 2016
Source:Cancer Epidemiology, Volume 41
Author(s): Nasreen Abdullah, Robert S. Laing, Susan Hariri, Collette M. Young, Sean Schafer
BackgroundHuman papillomavirus (HPV) vaccine should reduce cervical dysplasia before cervical cancer. However, dysplasia diagnosis is screening-dependent. Accurate screening estimates are needed.PurposeTo estimate the percentage of women in a geographic population that has had cervical cancer screening.MethodsWe analyzed claims data for (Papanicolau) Pap tests from 2008–2012 to estimate the percentage of insured women aged 18–39 years screened. We estimated screening in uninsured women by dividing the percentage of insured Behavioral Risk Factor Surveillance Survey respondents reporting previous-year testing by the percentage of uninsured respondents reporting previous-year testing, and multiplying this ratio by claims-based estimates of insured women with previous-year screening. We calculated a simple weighted average of the two estimates to estimate overall screening percentage. We estimated credible intervals using Monte-Carlo simulations.ResultsDuring 2008–2012, an annual average of 29.6% of women aged 18–39 years were screened. Screening increased from 2008 to 2009 in all age groups. During 2009–2012, the screening percentages decreased for all groups, but declined most in women aged 18–20 years, from 21.5% to 5.4%. Within age groups, compared to 2009, credible intervals did not overlap during 2011 (except age group 21–29 years) and 2012, and credible intervals in the 18–20 year group did not overlap with older groups in any year.ConclusionsThis introduces a novel method to estimate population-level cervical cancer screening. Overall, percentage of women screened in Portland, Oregon fell following changes in screening recommendations released in 2009 and later modified in 2012.



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The safety and validity of surgical resection for hemodialysis-dependent patients with renal cell carcinomas involving the inferior vena cava

Abstract

Perioperative morbidity and mortality increase during renal cell carcinoma resection with inferior vena cava involvement in hemodialysis-dependent end-stage renal disease patients. We evaluated the safety and validity of surgical management for renal cell carcinoma with inferior vena cava thrombi in such patients undergoing radical nephrectomies and tumor thrombectomies. There were three patients with tumor thrombus level II, and one each with tumor thrombus level III and IV. We evaluated median operative time (337 min), median estimated blood loss (1300 mL), and median postoperative hospitalization (15 days). Postoperative complications included surgical site dehiscence and pulmonary thromboembolism. One patient with preoperatively identified lung metastases developed a pulmonary thromboembolism on day 3 and died on day 15. The other four patients had long postoperative survival (19–104 months). Successful surgical management of renal cell carcinoma involving the inferior vena cava requires preoperative evaluation of the patient's condition to improve survival for hemodialysis-dependent end-stage renal disease patients.

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An 8-gene mRNA expression profile in circulating tumor cells predicts response to aromatase inhibitors in metastatic breast cancer patients

Abstract

Background

Molecular characterization of circulating tumor cells (CTC) is promising for personalized medicine. We aimed to identify a CTC gene expression profile predicting outcome to first-line aromatase inhibitors in metastatic breast cancer (MBC) patients. Methods: CTCs were isolated from 78 MBC patients before treatment start. mRNA expression levels of 96 genes were measured by quantitative reverse transcriptase polymerase chain reaction. After applying predefined exclusion criteria based on lack of sufficient RNA quality and/or quantity, the data from 45 patients were used to construct a gene expression profile to predict poor responding patients, defined as disease progression or death <9 months, by a leave-one-out cross validation.

Results

Of the 45 patients, 19 were clinically classified as poor responders. To identify them, the 75 % most variable genes were used to select genes differentially expressed between good and poor responders. An 8-gene CTC predictor was significantly associated with outcome (Hazard Ratio [HR] 4.40, 95 % Confidence Interval [CI]: 2.17–8.92, P < 0.001). This predictor identified poor responding patients with a sensitivity of 63 % and a positive predictive value of 75 %, while good responding patients were correctly predicted in 85 % of the cases. In multivariate Cox regression analysis, including CTC count at baseline, the 8-gene CTC predictor was the only factor independently associated with outcome (HR 4.59 [95 % CI: 2.11–9.56], P < 0.001). This 8-gene signature was not associated with outcome in a group of 71 MBC patients treated with systemic treatments other than AI.

Conclusions

An 8-gene CTC predictor was identified which discriminates good and poor outcome to first-line aromatase inhibitors in MBC patients. Although results need to be validated, this study underscores the potential of molecular characterization of CTCs.

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Systemic inflammation is an independent predictive marker of clinical outcomes in mucosal squamous cell carcinoma of the head and neck in oropharyngeal and non-oropharyngeal patients

Abstract

Background

Currently there are very few biomarkers to identify head and neck squamous cell carcinoma (HNSCC) cancer patients at a greater risk of recurrence and shortened survival. This study aimed to investigate whether a marker of systemic inflammation, the neutrophil-to-lymphocyte ratio (NLR), was predictive of clinical outcomes in a heterogeneous cohort of HNSCC cancer patients.

Methods

We performed a retrospective analysis to identify associations between NLR and clinicopathological features to recurrence free survival (RFS) and overall survival (OS). Univariate analysis was used to identify associations and selected variables were included in multivariable Cox regression analysis to determine predictive value.

Results

A total of 145 patients with stage I-IV HNSCC that had undergone radiotherapy were analysed. Seventy-six of these patients had oropharyngeal cancer and 69 had non-oropharyngeal HNSCC and these populations were analysed separately. NLR was not associated to any clinicopathological variable. On univariate analysis, NLR showed associations with RFS and OS in both sub-populations. Multivariable analysis showed patients with NLR > 5 had shortened OS in both sub-populations but NLR > 5 only predicted RFS in oropharyngeal patients. Poor performance status predicted OS in both sub-populations and current smokers had shortened OS and RFS in non-oropharyngeal patients.

Conclusions

The results show patients with NLR > 5 predict for shorter overall survival. Further prospective validation studies in larger cohorts are required to determine the clinical applicability of NLR for prognostication in HNSCC patients.

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Air pollution from traffic and risk for brain tumors: a nationwide study in Denmark

Abstract

Purpose

Air pollution is an established lung carcinogen, and there is increasing evidence that air pollution also negatively affects the brain. We have previously reported an association between air pollution and risk of brain tumors in a cohort study based on only 95 cases. We set out to replicate that finding in a large nationwide case–control study.

Methods

We identified all 4,183 adult brain tumor cases in Denmark in the years 2000–2009 and 8,018 risk set sampled population controls matched on gender and year of birth. We extracted residential address histories and estimated mean residential nitrogen oxides (NO_x ) concentrations since 1971 with a validated dispersion model. Categorical and linear odds ratios (OR) and confidence intervals (CI) were calculated with conditional logistic regression models.

Results

The highest risk estimates for any brain cancer were observed among subjects with the highest average exposure levels (80–99 µg/m³: OR 1.27, 95 % CI 0.82–1.96; ≥100 µg/m³: 1.40, 95 % CI 0.87–2.26 as compared to <20 µg/m³ NO_x ), but there was no increased OR at NO_x levels below 80 µg/m³ and when modeled linearly there was no significant association with risk of brain cancer (OR 1.11, 95 % CI 0.84–1.46 per 100 µg/m³ NO_x ). In sub-analysis the OR associated with exposures ≥100 µg/m³ was 2.30 (95 % CI 1.15–4.59) for non-glioma and 0.89 (95 % CI 0.44–1.77) for glioma.

Conclusions

This study did not support the relatively strong linear association between air pollution and risk of brain tumors which was found in our previous study. The suggestion of an increased brain tumor risk at high exposures merits further attention as does the differing results according to tumor morphology.

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Modeling how substitution of sedentary behavior with standing or physical activity is associated with health-related quality of life in colorectal cancer survivors

Abstract

Purpose

Previous research indicates that sedentary behavior is unfavorably associated with health-related quality of life (HRQoL) of colorectal cancer (CRC) survivors. Using isotemporal substitution modeling, we studied how substituting sedentary behavior with standing or physical activity was associated with HRQoL in CRC survivors, 2–10 years post-diagnosis.

Methods

A cross-sectional study was conducted in stage I–III CRC survivors (n = 145) diagnosed at Maastricht University Medical Center+, the Netherlands (2002–2010). Sedentary, standing, and physical activity time were measured by the thigh-mounted MOX activity monitor. HRQoL outcomes comprised global quality of life, physical, role, and social functioning, and disability (scales: 0–100), fatigue (20–140), and depression and anxiety (0–21). Isotemporal substitution modeling was applied to analyze associations with HRQoL of substituting sedentary time with equal time in standing or physical activity.

Results

On average, participants spent 10.2 h/day sedentary (SD, 1.7), 3.4 h/day standing (1.3), and 1.7 h/day in physical activity (0.8). In confounder-adjusted isotemporal models, substituting sedentary time with standing or with physical activity was associated with significantly better physical functioning (regression coefficient [β], i.e., difference in outcome score per 1 h/day of sedentary time substituted with standing or physical activity, 3.1; 95 % confidence interval [CI] 0.5, 5.7; and 5.6; 0.7, 10.6, respectively). Substituting sedentary time with standing was also associated with significantly lower disability (β, −3.0; 95 % CI −4.9, −1.1) and fatigue (−4.0; −7.6, −0.3).

Conclusions

Our results suggest that substituting sedentary behavior with standing or physical activity may be beneficially associated with certain HRQoL outcomes in CRC survivors. Prospective studies are warranted to confirm whether actual substitution of sedentary behavior with these activities may improve HRQoL in CRC survivors.

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Vaccination using melanoma cells treated with p19arf and interferon beta gene transfer in a mouse model: a novel combination for cancer immunotherapy

Abstract

Previously, we combined p19^Arf (Cdkn2a, tumor suppressor protein) and interferon beta (IFN-β, immunomodulatory cytokine) gene transfer in order to enhance cell death in a murine model of melanoma. Here, we present evidence of the immune response induced when B16 cells succumbing to death due to treatment with p19^Arf and IFN-β are applied in vaccine models. Use of dying cells for prophylactic vaccination was investigated, identifying conditions for tumor-free survival. After combined p19^Arf and IFN-β treatment, we observed immune rejection at the vaccine site in immune competent and nude mice with normal NK activity, but not in NOD-SCID and dexamethasone immunosuppressed mice (NK deficient). Combined treatment induced IL-15, ULBP1, FAS/APO1 and KILLER/DR5 expression, providing a mechanism for NK activation. Prophylactic vaccination protected against tumor challenge, where markedly delayed progression and leukocyte infiltration were observed. Analysis of primed lymphocytes revealed secretion of TH1-related cytokines and depletion protocols showed that both CD4⁺ and CD8⁺ T lymphocytes are necessary for immune protection. However, application of this prophylactic vaccine where cells were treated either with IFN-β alone or combined with p19^Arf conferred similar immune protection and cytokine activation, yet only the combination was associated with increased overall survival. In a therapeutic vaccine protocol, only the combination was associated with reduced tumor progression. Our results indicate that by harnessing cell death in an immunogenic context, our p19^Arf and IFN-β combination offers a clear advantage when both genes are included in the vaccine and warrants further development as a novel immunotherapy for melanoma.

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Neuroblastoma With Intraspinal Extension: Health Problems in Long-Term Survivors

Aim

To evaluate the prevalence of health problems in 5-year survivors treated for neuroblastoma (NBL) with intraspinal extension.

Patients and Methods

Retrospective, single center cohort study (using data from Childhood Cancer Registry and medical records) of patients treated for NBL with intraspinal extension (between 1980 and 2007) who survived ≥ 5 years after diagnosis. Health problems were graded according to the Common Terminology Criteria for Adverse Events (CTCAEv.3.0).

Results

All eligible patients (n = 19) were included (n = 7 no neurological symptoms at diagnosis), median age at diagnosis was 1.2 years (0.6–10.8 years), and median follow-up time was 15.6 years (6.3–29.5 years). Ninety-five percent of survivors had ≥1 health problem and 48% of survivors had ≥4 health problem with a mean of 3.8 per survivor. Fifty-three percent of survivors had at least one severe (grade 3) or life-threatening/disabling (grade 4) health problem. The three most prevalent health problems were kyphosis and/or scoliosis (68% of patients), motor neuropathy (32% of patients), and sensory neuropathy (26% of patients). Of the 13 patients who underwent a laminectomy, 54% (seven of 13) developed a grade 3 and 23% (three of 13) developed a grade 4 health problem. Among six patients, without laminectomy, 17% developed (one of six) a grade 3 and in 17% developed (one of six) a grade 4 health problem.

Conclusions

Ninety-five percent of 5-year survivors treated for a childhood intraspinal NBL have health problems. The high prevalence of grade 3 and 4 health problems (especially in the laminectomy group) emphasizes the importance of specialized long-term multidisciplinary follow-up and identifies optimal treatment with limited morbidity and maximal efficacy.

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Erratum to: ‘Phosphoproteomic analysis reveals Smarcb1 dependent EGFR signaling in Malignant Rhabdoid tumor cells’

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A comparison of heterosexual and LGBTQ cancer survivors’ outlooks on relationships, family building, possible infertility, and patient-doctor fertility risk communication

Abstract

Purpose

Little research about cancer-related infertility has examined the experiences and needs of lesbian, gay, bisexual, transgender, or queer (LGBTQ) cancer survivors. This research seeks to understand how LGBTQ survivors are similar to or different from heterosexual survivors with respect to cancer treatments' effects on relationships, plans for parenthood, and fertility preservation decision making.

Methods

Semi-structured telephone interviews conducted with adolescent or young adult (AYA) cancer survivors (n = 56) were coded for themes. Interviews consisted of questions about pre- and post-diagnosis thoughts about relationships, parenthood, possible infertility, and how information about fertility risks was received.

Results

While LGBTQ (n = 22) and heterosexual (n = 34) survivors reported similar challenges when dating post-diagnosis, heterosexual survivors were more likely to report fertility concerns as affecting romantic relationships (p < .05). LGBTQ survivors seemed more open to raising non-biological children or not becoming a parent than heterosexual survivors. LGBTQ survivors generally reported being satisfied with or indifferent to the information that they were given regarding fertility loss, despite reporting receiving similar amounts of information as compared to heterosexual patients (p < .10).

Conclusions

LGBTQ patients' views on relationships, parenthood, and family building seemed to result in less distress when faced with infertility. However, interventions facilitating information exchange about dating, fertility risks, and family building options may be valuable to LGBTQ and heterosexual cancer survivors.

Implications for Cancer Survivors

LGBTQ cancer survivors may display more adaptive coping with respect to relationships and fertility loss. Oncology professionals may want to proactively introduce positive coping strategies to reduce distress among AYA cancer survivors at risk for infertility.

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Quantitative accuracy of 177 Lu SPECT reconstruction using different compensation methods: phantom and patient studies

Abstract

Background

In targeted radionuclide therapy (TRT), accurate quantification using SPECT/CT images is important for optimizing radiation dose delivered to both the tumour and healthy tissue. Quantitative SPECT images are regularly reconstructed using the ordered subset expectation maximization (OSEM) algorithm with various compensation methods such as attenuation (A), scatter (S) and detector and collimator response (R). In this study, different combinations of the compensation methods are applied during OSEM reconstruction and the effect on the ¹⁷⁷Lu quantification accuracy is studied in an anthropomorphic torso phantom. In addition, the phantom results are reflected to (177)Lu-DOTA-Tyr3-octreotate (¹⁷⁷Lu-DOTATATE)-treated patient data and kidney absorbed dose estimates.

Methods

The torso phantom was imaged with nine various sized (0.4–104.4 cm³) spherical inserts, filled with known ¹⁷⁷Lu activity ranging from 0.5 to 105.5 MBq. Images were reconstructed using OSEM algorithm using A, AR and ARS compensation method combinations. The compensation method combinations were compared by calculating the concentration recovery coefficient (cRC) for each insert. In addition, ten ¹⁷⁷Lu-DOTATATE-treated patient's post-therapy dosimetry acquisitions were reconstructed, and the absorbed dose to kidneys was estimated.

Results

cRC values depend on the insert size for all compensation methods. AR and ARS produced significantly higher cRC values than attenuation correction alone. There were no cRC value differences between the methods for the smallest 1-cm-diameter insert, cRC being 0.18. However, the collimator and detector response compensation method (R) made the 1.3-cm-diameter insert clearly visible and improved cRC estimate from 0.19 to 0.43. ARS produced slightly higher cRC values for small- and medium-sized inserts than AR. On the patient data, a similar trend could be seen. AR and ARS produced higher kidney activities than using attenuation correction alone; the total absorbed doses to the right and left kidneys were on average 15 and 20 % higher for AR and 19 and 25 % higher for ARS, respectively. The effective half-life decay estimated from time-activity curves however showed no notable difference between the compensation methods.

Conclusions

The highest cRC values were achieved by applying ARS compensation during reconstruction. The results were notably higher than those using attenuation correction alone. Similarly, higher activity estimates and thus higher absorbed dose estimates were found in patient data when all compensation methods were applied. ARS improved cRC especially in small-sized sources, and it thus might aid tumour dosimetry for ¹⁷⁷Lu PRRT treatments.

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Ramucirumab Clinical Development: an Emerging Role in Gastrointestinal Tumors

Abstract

Ramucirumab (IMC-1121B, LY3009806) is a fully human G1 monoclonal antibody that specifically targets vascular endotelial growth factor receptor 2 (VEGFR-2) with a substantially greater binding affinity than that of its natural ligands. Early clinical trials in patients with advanced solid tumors demonstrated that biologically relevant blood target concentrations are achievable with tolerable doses, and also showed some preliminary evidence of clinical activity. Several pivotal phase III trials have now been concluded and have led regulatory agencies to grant marketing authorization to ramucirumab for use as second line therapy in patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma (as single agent or in combination with paclitaxel), in patients with advanced colorectal carcinoma (CRC) (in combination with infusional fluorouracil and irinotecan (FOLFIRI regimen)) and in patients with advanced non-small cell lung cancer (NSCLC) (in combination with docetaxel). In contrast, ramucirumab failed to significantly improve survival versus placebo as second line therapy in patients with advanced hepatocellular carcinoma (HCC). The aim of this review is to summarize the clinical development and emerging role of ramucirumab in gastrointestinal (GI) tumors, including relevant aspects of its mechanism of action, pharmacology, safety profile, and antitumor activity in gastric, HCC, and CRC carcinomas.

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Metastatic malignant melanoma in a young adult with unknown primary

AS Shenoy, HM Desai, VS Kavishwar, HV Savant

Indian Journal of Cancer 2015 52(3):446-447



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Primary chondrosarcoma in the young

BN Gayathri, TN Suresh, ML Harendra Kumar, HS Arun

Indian Journal of Cancer 2015 52(3):260-261



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Nasopharyngeal cancers: A retrospective comparative analysis of radiotherapy alone versus chemo-radiation (Benghazi experience)

A Pakkirmasthan, S Kurakula

Indian Journal of Cancer 2015 52(3):391-395

Introduction: Cancer of Nasopharynx is an important disease in Maghreb region. 75 patients (4.3%) of cancer nasopharynx between the years 1995 to 2000 were referred to our centre in Benghazi out of total 1757 patients. This study was done to analyze the clinical presentations and to study response to the treatment practiced. Materials And Methods: 59 patients were available with full records excluding the recurrent and metastatic presentation. 37 were males with 22 females (1.7:1), (31/59) 52% patients were from 25-49 years, (17/59) 28.8% were from 50-60 years. 44/59 (74%) patients presented with Lymphadenopathy either unilateral or bilateral. 46/59 (78%) of patients were in clinical stage II or III. 44/59 (74%) of patients were of undifferentiated histology. Results: The pattern of clinical response and trend of follow up those that received neoadjuvant chemotherapy and radiotherapy and radiotherapy alone are discussed. Discussion : In our analysis, we also found that the patients who had received chemotherapy by and large had a less trend to towards developing metastatic disease and local recurrence and faired better. Conclusion: We are now following the protocol of Neoadjuvant chemotherapy followed by chemo-radiotherapy and followed by chemotherapy and results will mature in the years to come.

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Single-walled and multi-walled carbon nanotubes based drug delivery system: Cancer therapy: A review

B Dineshkumar, K Krishnakumar, AR Bhatt, D Paul, J Cherian, A John, S Suresh

Indian Journal of Cancer 2015 52(3):262-264

Carbon nanotubes (CNTs) are advanced nano-carrier for delivery of drugs especially anti-cancer drugs. In the field of CNT-based drug delivery system, both single-walled carbon nanotubes (SWCNTs) and multi-walled nanotubes (MWCNTs) can be used for targeting anticancer drugs in tissues and organs, where the high therapeutic effect is necessary. Benefits of the carbon nanotubes (CNTs) in drug delivery systems are; avoiding solvent usage and reducing the side effects. Therefore, the present review article described about achievement of SWCNTs and MWCNTs to deliver the anticancer drugs with different cancerous cell lines.

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Cystosarcoma phyllodes: Pathological enigma: A retrospective review of 162 cases

RP Narayanakar, DM Gangaiah, S Althaf, K Dev, V Kurpad, J Gurawalia

Indian Journal of Cancer 2015 52(3):365-368

Purpose: Phyllodes tumor (PT) is a rare fibroepithelial neoplasm comprising <1% of all breast tumors. Clinical spectrum ranges from benign (B), borderline (BL), and locally recurrent to malignant (M) and metastatic type. The aim of our study was to analyze the clinicopathological factors, compare treatment options, and evaluate outcome in patients with PT. Methods: We retrospectively reviewed 162 women with PT. The surgical intervention varied from simple excision (lumpectomy)/wide local excision (WLE) in benign cases to simple/modified radical or radical mastectomy (SM/MRM/RM) in malignant and recurrent tumors. Results: Out of 162 patients, B, BL, and M were 95 (58.64%), 29 (18%), and 38 (23.45%), respectively. Mean age, duration of lump, and size were 38 ± 8 years, 28 ± 10 months, and 12 ± 5 cm, respectively. Recurrence rate with B, BL, and M was 15.78%, 41.37%, and 55.26%, respectively (P = 0.00001). As compared to WLE (22%), SM (23.8%), and MRM/RM (14.2%), recurrence was higher with lumpectomy (48.9%) (P = 0.004). Positive correlation was found between recurrence rate with the size of tumor (P = 0.008) and also number of recurrence with holoprosencephaly (P = 0.047). There was no association between the number of recurrences and size of tumor (P = 0.63). Malignant PT was seen in 38 (24%) and distant metastasis was seen in 7 (18%). Mean duration of follow-up was 42 months. Conclusion: WLE with negative margins should be the initial surgery for PT. The role of adjuvant radiotherapy and chemotherapy is uncertain. PT is pathological enigma. Till date, no factors can accurately predict the recurrence and outcome. PT is known for unpredictable behavior and high recurrence rates, hence long-term follow-up is advised.

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Advanced prostate cancer presenting as bilateral testicular hydrocele

S Gupta, A Mehta, J Kaur

Indian Journal of Cancer 2015 52(3):264-265



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Neoadjuvant chemotherapy and surgery versus surgery alone in resectable esophageal cancer

K Bushan, S Sharma

Indian Journal of Cancer 2015 52(3):413-416

The aim of this article is to review randomized and non-randomized trials and meta-analysis comparing neoadjuvant chemotherapy (NAC) plus surgery versus surgery alone in resectable esophageal cancers. The article examines the value of NAC as a standard of care in the era of multimodality treatment with availability of different therapeutic options. The emphasis is on assessment of benefit of NAC in terms of survival (long and short term) rate of RO resection in resectable esophageal cancers of any histopathologic type. The in-hospital post-operative morbidity and mortality in NAC group, chemotherapeutic drug regimens and their response rates and optimal number of cycles to be used will also be addressed

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Dual surrogate markers for rapid prediction of epidermal growth factor receptor mutation status in advanced adenocarcinoma of the lung: A novel approach in resource-limited setting

KS Udupa, R Rajendranath, TG Sagar, S Sundersingh, T Joseph

Indian Journal of Cancer 2015 52(3):266-268

Introduction: Tyrosine kinase inhibitors have revolutionized the treatment of metastatic lung cancer in patients with epidermal growth factor receptor (EGFR) mutations. Amplified refractory mutation system (ARMS)-reverse transcription-polymerase chain reaction (RT-PCR), the current standard for detecting EGFR mutation status is time-consuming and highly expensive. Consequently any surrogate test which are cheaper, faster and as accurate as the PCR method will help in early diagnosis and management of patients with lung cancer, especially in resource-limited settings. Materials and Methods: Eighty-five patients, all of South Indian origin, with adenocarcinoma of lung, registered between October 2009 and January 2013, were evaluated for EGFR mutation status by using scorpion probe based ARMS RT-PCR method. Immunohistochemical (IHC) was performed using the phosphorylated AKT (P-AKT) and thyroid transcription factor-1 (TTF-1) on above patient's sample, and the results were compared with EGFR mutation tests. Results: EGFR mutation was positive in 34 of 85 patients (40%). P-AKT and TTF-1 were positive in 50 (58.8%) and 68 (80%) patients respectively. Both P-AKT and TTF-1 had statistically significant correlation with EGFR mutation status. Positive and negative predictive value of P-AKT in diagnosing EGFR mutation was 58% and 85.5% and that for TTF-1 was 48.5% and 94.1%, respectively. The problem of low positive predictive value can partly be overcome by testing P-AKT and TTF-1 simultaneously. Conclusion: P-AKT and TTF-1 using IHC had statistically significant correlation with EGFR mutation with high negative predictive value. In the case of urgency of starting treatment, EGFR mutation testing may be avoided in those patients who are negative for these IHC markers and can be started on chemotherapy.

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Mixed germ cell tumor in a teenager: A rare entity

CR Choudhury, N Bhattacharya, TD Bhutia, M Mondal

Indian Journal of Cancer 2015 52(3):470-472



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Epigenetic Modulators and the New Immunotherapies

The recent arrival of the immune-checkpoint–inhibitor drugs — first applied to melanoma and more recently tested as a treatment for different solid tumors and hematologic cancers — has changed the management of these conditions. The response rates have been impressive, as have the…

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Healthcare professionals' views on discussing fertility preservation with young cancer patients: a mixed method systematic review of the literature

Abstract

Objective

In spite of efforts to guarantee patients are adequately informed about their risk of fertility loss and offered treatment for fertility preservation (FP), previous studies have reported that this topic is not routinely discussed with patients, especially with younger patient populations. A mixed method systematic review was undertaken to explore the factors shaping the discussion of FP with children (0–15 years) and adolescents/young adults (16–24 years) with cancer.

Methods

Six databases were searched independently using a combination of keywords and controlled vocabulary/subject headings relating to cancer and fertility. Inclusion criteria consisted of: (a) being published in a peer-reviewed journal, (b) a focus on healthcare professionals' (HCPs') beliefs, attitudes, or practices regarding fertility issues in cancer patients, (c) primary data collection from HCPs, and (d) a focus on HCPs who provide services to young patients. Of the 6276 articles identified in the search, 16 articles presenting the results of 14 studies were included in the final review.

Results

Common themes reported across studies indicate that five main factors influence HCPs' discussion of FP with young cancer patients: (a) HCPs' knowledge, (b) HCPs' sense of comfort, (c) patient factors (i.e., sexual maturity, prognosis, partnership status, and whether or not they initiate the conversation), (d) parent factors (i.e., HCPs' perception of the extent of their involvement), and (e) availability of educational materials.

Conclusions

Future work should ensure that HCPs possess knowledge of cancer-related FP and that they receive adequate training on how to consent and discuss information with young patients and their parents.

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The role of social–cognitive and emotional factors on testicular self-examination

Abstract

Objective

This study determined the role of social–cognitive and affective factors in promoting testicular self-examination.

Methods

Male participants (N = 115) rated their perceptions of testicular cancer, social–cognitive variables (attitude, subjective norm, and perceived control), and their emotions towards testicular cancer (anxiety and shame) and testicular self-examination (anticipated regret and relief). Participants also stated whether or not they had performed a testicular self-examination within the last month.

Results

Perceived control and anticipated relief positively predicted testicular self-examination within the last month. Both these factors also positively predicted the intention to self-examine in the future. Intention was also positively predicted by attitude and negatively predicted by shame.

Conclusions

These results highlight the importance of social–cognitive and emotional factors in promoting health screening. Targeting these factors might improve the effectiveness of testicular self-examination interventions. Copyright © 2016 John Wiley & Sons, Ltd.

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Stage I and II Endometrial Adenocarcinoma: Analysis of 2009 FIGO Staging Revision and Impact on Survival by Adjuvant Therapy.

Background: In 2009, the International Federation of Gynecology and Obstetrics revised the staging classification for endometrial cancer. Mucosal cervical involvement was eliminated from the criteria and only those with stromal cervical involvement were considered stage II. We examined the implications of the staging changes and the survival impact of adjuvant therapy in stage I to II endometrial adenocarcinoma. Materials and Methods: Data were obtained from the National Oncology Data Alliance. Stage I to II endometrial adenocarcinoma patients diagnosed between 1988 and 2008 were identified and grouped according to the 1988 International Federation of Gynecology and Obstetrics staging. Multivariate analysis (MVA) was performed using proportional hazards model; comparison of Kaplan-Meier survival curves was based on the log-rank statistic. Results: A total of 14,158 patients with stage I to II endometrial adenocarcinoma were identified with a median follow-up of 41 months. Adjuvant external-beam radiation therapy (EBRT) and adjuvant vaginal brachytherapy (VB) were positive predictors for overall survival (OS) only in IC, IIA, and IIB. On MVA, stages IA and IB OS did not differ (P=0.17), IIA had worse OS compared with IC (P

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Phase I Trial of Dose-escalated Whole Liver Irradiation With Hepatic Arterial Fluorodeoxyuridine/Leucovorin and Streptozotocin Followed by Fluorodeoxyuridine/Leucovorin and Chemoembolization for Patients With Neuroendocrine Hepatic Metastases.

Objectives: We have previously shown that refractory neuroendocrine tumors can respond to moderate doses of chemoradiotherapy. We completed a dose-escalation phase I/II trial combining hepatic arterial (HA) chemotherapy, chemoembolization, and dose-escalated whole liver radiotherapy to determine the maximum safe dose of radiation that could be delivered and to make a preliminary assessment of response. Materials and Methods: From 2002 to 2009, 19 patients with symptomatic neuroendocrine liver metastases who failed somatostatin analog therapy were enrolled. HA fluorodeoxyuridine, leucovorin, and streptozotocin were delivered, as concurrent whole liver radiotherapy was dose escalated from 24 to 32 Gy in 2 Gy fractions, with a target rate of dose-limiting grade >=3 radiation-induced liver disease of 10%. Eight weeks later, for patients without grade >=3 liver or grade >=4 any toxicity, a 72-hour infusion of HA fluorodeoxyuridine and leucovorin was given, followed by transarterial chemoembolization. Results: Eleven patients completed the entire protocol and received 24 to 32 Gy. No patients developed radiation-induced liver disease; 7 had grade 3 to 4 transiently increased liver function tests, and 4 had other grade 4 toxicities. Three patients (14%) had partial response, 16 (84%) stable disease. Median freedom from local progression and overall survival were 35.3 and 54.6 months, respectively. Conclusions: Thirty-two in 2 Gy daily fractions can be delivered safely when combined with HA chemotherapy and subsequent transarterial chemoembolization. However, although objective responses were observed, this combination was not significantly better than our prior approaches. Further treatment intensification strategies, including individualized dose escalation for radiation-tolerant livers, and improved radiosensitization should be investigated, along with improved systemic therapy. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Medicare Cancer Screening in the Context of Clinical Guidelines: 2000 to 2012.

Objectives: Cancer screening is a ubiquitous and controversial public health issue, particularly in the elderly population. Despite extensive evidence-based guidelines for screening, it is unclear how cancer screening has changed in the Medicare population over time. We characterize trends in cancer screening for the most common cancer types in the Medicare fee-for-service (FFS) program in the context of conflicting guidelines from 2000 to 2012. Materials and Methods: We performed a descriptive analysis of retrospective claims data from the Medicare FFS program based on billing codes. Our data include all claims for Medicare part B beneficiaries who received breast, colorectal (CRC), or prostate cancer screening from 2000 to 2012 based on billing codes. We utilize a Monte Carlo permutation method to detect changes in screening trends. Results: In total, 231,416,732 screening tests were analyzed from 2000 to 2012, representing an average of 436.8 tests per 1000 beneficiaries per year. Mammography rates declined 7.4%, with digital mammography extensively replacing film. CRC cancer screening rates declined overall. As a percentage of all CRC screening tests, colonoscopy grew from 32% to 71%. Prostate screening rates increased 16% from 2000 to 2007, and then declined to 7% less than its 2000 rate by 2012. Discussion: Both the aggressiveness of screening guidelines and screening rates for the Medicare FFS population peaked and then declined from 2000 to 2012. However, guideline publications did not consistently precede utilization trend shifts. Technology adoption, practical and financial concerns, and patient preferences may have also contributed to the observed trends. Further research should be performed on the impact of multiple, conflicting guidelines in cancer screening. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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A Meta-Analysis of the Association Between Radiation Therapy and Survival for Surgically Resected Soft-Tissue Sarcoma.

Objectives: Radiotherapy for soft-tissue sarcoma (STS) has been shown to reduce local recurrence, but without clear improvement in survival. We conducted a meta-analysis to study the association between radiotherapy and survival in patients undergoing surgery for STS. Methods: A systematic review was conducted from PubMed, EMBASE, Web of Science, and Cochrane databases. Our population of interest consisted of adults with primary extremity, chest wall, trunk, or back STS. Our metameters were either an odds or hazard ratio for mortality. A bias score was generated for each study based on margin status and grade. Results: Of 1044 studies, 30 met inclusion criteria for final analysis. The pooled odds ratio in patients receiving radiation was 0.94 (95% confidence interval [CI], 0.78-1.14). The pooled estimate of the hazards ratio in patients receiving radiation was 0.87 (95% CI, 0.73-1.03) overall and 0.65 (95% CI, 0.52-0.82) for studies judged to be at low risk of bias. Significant publication bias was not seen. Conclusions: High-quality studies reporting adjusted hazard ratios are associated with improved survival in patients receiving radiotherapy for STS. Studies in which odds ratios are calculated from event data and those that do not report adjusted outcomes do not show the same association, likely due to confounding by indication. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Pre-ESRD Care and Mortality in Incident ESRD Patients With Multiple Myeloma.

Objectives: The relationship between mortality and pre-ESRD (end-stage renal disease) nephrology care in incident ESRD patients with multiple myeloma (MM) as the primary cause of renal failure has not been examined. Materials and Methods: Among 439,206 incident US hemodialysis patients with MM as the primary cause of ESRD (June 1, 2005 to May 31, 2009) identified using the US Renal Data System, adjusted odds ratios (OR) for reported pre-ESRD nephrology care for ESRD due to MM (n=4561) versus other causes (n=434,645) were calculated. The association of pre-ESRD nephrology care with subsequent mortality in MM-ESRD patients was examined. Results: MM-ESRD patients were less likely to have any predialysis nephrology care in the year before initiation of dialysis (34.8% vs. 58.5%; OR=0.38; 95% confidence interval [CI], 0.34-0.43) compared with patients with ESRD due to other causes. MM-ESRD patients compared with others were more likely to have catheters on first dialysis (91.8% vs. 75.6%; OR=4.15; 95% CI, 3.54-4.86). Incident MM-ESRD patients receiving predialysis care for >=6 months had significantly lower 1-year mortality (hazard ratio 0.89; 95% CI, 0.82-0.97 and 0.88; 95% CI, 0.80-0.96, respectively), relative to those without this care. A catheter for dialysis access was associated with a 1.6-fold increase in 1-year mortality in incident MM-ESRD (hazard ratio 1.55; 95% CI, 1.32-1.83). Conclusions: MM-ESRD patients were less likely to have predialysis nephrology care and more likely to use catheters on first dialysis. However, predialysis care is independently associated with lower mortality in MM-ESRD patients. Predialysis care should be prioritized in MM patients approaching ESRD. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Anatomical liver resection of segment 4a en bloc with the caudate lobe

Anatomical segmentectomy is the complete resection of an area supplied by a segmental portal branch. Among segmentectomies, isolated segmentectomy 4 is a technically demanding procedure because there are two transection planes: on the left side along the umbilical fissure and, on the right side, along the middle hepatic vein. Although there are several reports on anatomic segmentectomies, only few regard the anatomic segmentectomy 4a. We report here the case of a 60-year-old man who underwent anatomical segmentectomy 4a en bloc with the caudate lobe to resect a colorectal liver metastasis located in segment 4a and involving the paracaval portion of the caudate lobe. This type of procedure was planned in order to maximize the postoperative functional hepatic reserve, thereby reducing the risk of postoperative liver failure and ultimately allowing the possibility for future repeat hepatectomy in case of recurrence. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

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First-line therapy for treatment-naive patients with advanced/metastatic renal cell carcinoma: a systematic review of published randomized controlled trials.

In the recent years, a number of targeted therapies have been approved for first-line treatment of patients with metastatic renal cell carcinoma. A systematic review was conducted to assess the clinical efficacy, safety and effect of all first-line treatments evaluated to date on health-related quality of life (HRQoL). A systematic search of Embase, Cochrane and MEDLINE databases was performed to identify randomized controlled trials (1980-2015) evaluating any targeted therapy/immunotherapy against placebo or any other targeted intervention/immunotherapy in treatment-naive patients with metastatic renal cell carcinoma. Conference proceedings from major cancer congresses (2007-2015) were handsearched. Sixteen randomized controlled trials were identified, mostly phase III. Overall, targeted therapies were associated with either improved [sunitinib, bevacizumab+interferon [alpha] (IFN[alpha]) and temsirolimus] or comparable (sorafenib) progression-free survival (PFS) versus IFN[alpha] monotherapy. Sunitinib demonstrated comparable PFS and overall survival to pazopanib, comparable PFS to sorafenib and shorter PFS compared with bevacizumab+IFN[alpha] (although no conclusions were made with regard to superiority/inferiority). Compared with sorafenib, tivozanib demonstrated a significantly longer PFS, and both tivozanib and axitinib demonstrated higher response rates. Nintedanib demonstrated comparable PFS and overall survival to sunitinib in a phase II trial. Temsirolimus, sunitinib and sorafenib treatment led to better HRQoL versus IFN[alpha]; pazopanib was associated with better HRQoL versus sunitinib. No direct meta-analyses or indirect treatment comparison analysis were undertaken because of noncomparability of the trials. In general, targeted therapies demonstrated favourable clinical efficacy and improved HRQoL compared with IFN[alpha] monotherapy. The newer therapies, tivozanib and axitinib (but not nintedanib), appeared to exhibit greater clinical benefit (response rate) than older tyrosine kinase inhibitors. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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