Targeting homologous recombination in glioma chemotherapy

Malignant gliomas exhibit a high level of intrinsic and acquired drug resistance and have a dismal prognosis. First and second line therapeutics for glioblastomas are alkylating agents, including the chloroethylating nitrosoureas (CNUs) lomustine, nimustine, fotemustine and carmustine. These agents target the tumor DNA, forming O6-chloroethylguanine adducts and secondary DNA interstrand crosslinks (ICLs). These crosslinks are supposed to be converted into DNA double-strand breaks, which trigger cell death pathways. Here, we show that lomustine (CCNU) with moderately toxic doses induces ICLs in glioblastoma cells, inhibits DNA replication fork movement and provokes the formation of DSBs and chromosomal aberrations. Since homologous recombination (HR) is involved in the repair of DSBs formed in response to CNUs, we elucidated whether pharmacological inhibitors of HR might have impact on these endpoints and enhance the killing effect. We show that the Rad51 inhibitors RI-1 and B02 greatly ameliorate DSBs, chromosomal changes and the level of apoptosis and necrosis. We also show that an inhibitor of MRE11, mirin, which blocks the formation of the MRN complex and thus the recognition of DSBs, has a sensitizing effect on these endpoints as well. In a glioma xenograft model, the Rad51 inhibitor RI-1 clearly enhanced the effect of CCNU on tumor growth. The data suggests that pharmacological inhibition of HR, e.g. by RI-1, is a reasonable strategy for enhancing the anticancer effect of CNUs.

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In vivo antitumor Activity of a Recombinant IL-7/IL-15

Both IL-7 and IL-15 have become important candidate immunomodulators for cancer treatment. However, IL-7 or IL-15 used alone suffers from shortcomings, such as short serum half-life and limited antitumor effect. We have cloned and expressed a recombinant (r) IL-7/IL-15 fusion protein in which IL-7 and IL-15 are linked by a flexible linker. We then compared the antitumor effect of rIL-7/IL-15 with the individual factors rIL-7 and/or rIL-15. We show here that rIL-7/IL-15 has a higher antitumor activity than the combination of the individual factors in both murine B16F10 melanoma and CT-26 colon cancer models. This was associated with a significant increase in tumor infiltration of T cells, DCs and NK cells and a decrease in regulatory T cells (Tregs). In addition, rIL-7/IL-15-treated DCs had higher expression of costimulatory molecules CD80 and CD86. The higher antitumor activity of rIL-7/IL-15 is likely due to its longer in vivo half-life and different effects on immune cells. Our results suggest that rIL-7/IL-15 may offer a new tool to enhance antitumor immunity and treat cancer.

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Imatinib changes collagen structure and increases transport

A typical obstacle to cancer therapy is the limited distribution of low-molecular weight anti-cancer drugs within the carcinoma tissue. In experimental carcinoma, Imatinib (STI571) increases efficacy of synchronized chemotherapy, reduces tumor interstitial fluid pressure and increases interstitial fluid volume. STI571 also increases the water-perfusable fraction in metastases from human colorectal adenocarcinomas. Because the mechanism(s) behind these effects have not been fully elucidated, we investigated the hypothesis that STI571 alters specific properties of the stromal extracellular matrix. We analyzed STI571-treated human colorectal KAT-4/HT-29 experimental carcinomas, known to have a well-developed stromal compartment, for solute exchange and glycosaminoglycan content, as well as collagen content, structure and synthesis. Magnetic resonance imaging of STI571-treated KAT-4/HT-29 experimental carcinomas showed a significantly increased efficacy in dynamic exchanges of solutes between tumor interstitium and blood. This effect was paralleled by a distinct change of the stromal collagen network architecture, manifested by a decreased average collagen fibril diameter and increased collagen turnover. The glycosaminoglycan content was unchanged. Furthermore, the apparent effects on the stromal cellular composition were limited to a reduction in a NG2-positive stromal cell population. The present data support the hypothesis that the collagen network architecture influences the dynamic exchanges of solutes between blood and carcinoma tissue. It is conceivable that STI571 reprograms distinct non-vascular stromal cells to produce a looser extracellular matrix, ultimately improving transport characteristics for traditional chemotherapeutic agents.

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Wedelolactone interrupts c-Myc oncogenic signaling

The c-Myc gene encodes an oncoprotein transcription factor which is frequently up-regulated in almost all cancer types, and is the subject of intense investigation for management of cancer because of its pleiotropic effects controlling a spectrum of cellular functions. However, due of its non-enzymatic nature, development of suitable strategies to block its protein-protein or protein-DNA interaction is challenging. Thus, c-Myc has been recognized as an elusive molecular target for cancer control and various approaches are in development to inhibit c-Myc-transcriptional activity. We observed that wedelolactone (WDL), an anti-inflammatory botanical compound, severely down-regulates the expression of c-Myc mRNA in prostate cancer cells. Moreover, WDL dramatically decreases the protein level, nuclear localization, DNA-binding, and transcriptional activities of c-Myc. c-Myc is a transforming oncogene widely expressed in prostate cancer cells and is critical for maintaining their transformed phenotype. Interestingly, WDL was found to strongly affect the viability of Myc-activated prostate cancer cells, and completely blocks their invasion as well as soft-agar colony-formation in vitro. WDL was also found to down-regulate c-Myc in vivo in nude mice xenografts. Moreover, WDL synergizes with enzalutamide to decrease the viability of androgen-sensitive prostate cancer cells via induction of apoptosis. These findings reveal a novel anticancer mechanism of the natural compound, WDL, and suggest that the oncogenic function of c-Myc in prostate cancer cells can be effectively down-regulated by WDL for the development of a new therapeutic strategy against Myc-driven prostate cancer.

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FLIP-mediated radio-resistance in NSCLC

Resistance to radiotherapy due to insufficient cancer cell death is a significant cause of treatment failure in non-small cell lung cancer (NSCLC). The endogenous caspase-8 inhibitor, FLIP, is a critical regulator of cell death that is frequently overexpressed in NSCLC and is an established inhibitor of apoptotic cell death induced via the extrinsic death receptor pathway. Apoptosis induced by ionizing radiation (IR) has been considered to be mediated predominantly via the intrinsic apoptotic pathway; however, we found that IR-induced apoptosis was significantly attenuated in NSCLC cells when caspase-8 was depleted using RNA interference (RNAi), suggesting involvement of the extrinsic apoptosis pathway. Moreover, overexpression of wild-type FLIP, but not a mutant form that cannot bind the critical death receptor adaptor protein FADD, also attenuated IR-induced apoptosis, confirming the importance of the extrinsic apoptotic pathway as a determinant of response to IR in NSCLC. Importantly, when FLIP protein levels were down-regulated by RNAi, IR-induced cell death was significantly enhanced. The clinically relevant histone deacetylase (HDAC) inhibitors vorinostat and entinostat were subsequently found to sensitize a subset of NSCLC cell lines to IR in a manner that was dependent on their ability to suppress FLIP expression and promote activation of caspase-8. Entinostat also enhanced the anti-tumor activity of IR in vivo. Therefore, FLIP down-regulation induced by HDAC inhibitors is a potential clinical strategy to radio-sensitize NSCLC and thereby improve response to radiotherapy. Overall, this study provides the first evidence that pharmacological inhibition of FLIP may improve response of NCSLC to IR.

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CNDAC drug combinations

CNDAC (2'-C-cyano-2'-deoxy-1-β-D-arabino-pentofuranosyl-cytosine, DFP10917) and its orally bioavailable prodrug, sapacitabine, are undergoing clinical trials for hematological malignancies and solid tumors. The unique action mechanism of inducing DNA strand breaks distinguishes CNDAC from other deoxycytidine analogs. To optimize the clinical potentials of CNDAC, we explored multiple strategies combining CNDAC with chemotherapeutic agents targeting distinct DNA damage repair pathways that are currently in clinical use. The ability of each agent to decrease proliferative potential, determined by clonogenic assays, was determined in paired cell lines proficient and deficient in certain DNA repair proteins. Subsequently each agent was used in combination with CNDAC at fixed concentration ratios. The clonogenicity was quantitated by median effect analysis, and a combination index was calculated. The c-Abl kinase inhibitor, imatinib, had synergy with CNDAC in HCT116 cells, regardless of p53 status. Inhibitors of PARP1 that interfere with homologous recombination (HR) repair or base excision repair (BER) and agents such as temozolomide that cause DNA damage repaired by the BER pathway were also synergistic with CNDAC. The toxicity of the nitrogen mustards, bendamustine and cytoxan, or of platinum compounds, which generate DNA adducts repaired by nucleotide excision repair and HR, was additive with CNDAC. An additive cell killing was also achieved by the combination of CNDAC with taxane mitotic inhibitors (paclitaxel and docetaxel). At concentrations which allow survival of the majority of wild type cells, the synergistic or additive combination effects were selective in HR-deficient cells. This study provides mechanistic rationales for combining CNDAC with other active drugs.

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Repression of phosphoglycerate dehydrogenase sensitizes triple-negative breast cancer to doxorubicin

Abstract

Purpose

Approximately 70 % of triple-negative breast cancer (TNBC) cell lines are identified to upregulate phosphoglycerate dehydrogenase (PHGDH), which regulates the intracellular synthesis of serine and glycine, and promotes tumor growth. In this work, the impact of this pathway on doxorubicin efficacy was evaluated.

Methods

MDA-MB-468, BT-20 and HCC70 cells were transfected with lentiviral vectors expressing short hairpin RNA (shRNA) against PHGDH. In response to doxorubicin treatment, cellular proliferation was measured, ROS were evaluated and intracellular levels of serine, glycine and glutathione (GSH) were determined using liquid chromatography–mass spectrometry. A TNBC orthotopic tumor model was used to examine the effect of PHGDH on doxorubicin efficacy in vivo.

Results

TNBC cells exposed to doxorubicin undergo metabolic remodeling, resulting in increased glucose flux for serine synthesis regulated by PHGDH. Serine is then converted into GSH, which counters doxorubicin-induced formation of ROS. Consequently, suppression of PHGDH by the use of the shRNA caused doxorubicin-induced oxidative stress and increased doxorubicin sensitivity. The enhancement of doxorubicin efficacy through simultaneous suppression of PHGDH was validated in a mouse tumor model.

Conclusion

These results shed light on PHGDH that could be a promising target for increasing the effectiveness of chemotherapy in patients with TNBC.

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The 5th World Symposium for Lymphedema Surgery

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Total and mutated EGFR quantification in cell-free DNA from non-small cell lung cancer patients detects tumor heterogeneity and presents prognostic value

Abstract

Mutation analysis of epidermal growth factor receptor (EGFR) gene is essential for treatment selection in non-small cell lung cancer (NSCLC). Analysis is usually performed in tumor samples. We evaluated the clinical utility of EGFR analysis in plasma cell-free DNA (cfDNA) from patients under treatment with EGFR inhibitors. We selected 36 patients with NSCLC and EGFR-activating mutations. Blood samples were collected at baseline and during treatment with EGFR inhibitors. Wild-type EGFR, L858R, delE746-A750, and T790M mutations were quantified in cfDNA by droplet digital PCR. Stage IV patients had higher total circulating EGFR copy levels than stage I (3523 vs. 1003 copies/mL; p < 0.01). There was high agreement for activating mutations between baseline cfDNA and tumor samples, especially for L858R mutation (kappa index = 0.679; p = 0.001). In 34 % of advanced NSCLC patients, we detected mutations in cfDNA not previously detected in tumor samples and double mutations in 17 %. Patients with baseline total EGFR copy levels above the median presented decreased overall survival (OS) (341 vs. 870 days, p < 0.05) and progression-free survival (PFS) (238 vs. 783 days; p < 0.05) compared with those with total EGFR copy levels below the median. Patients with baseline concentrations of activating mutations above the median (94 copies/mL) had lower OS (317 vs. 805 days; p < 0.05) and PFS (195 vs. 724 days; p < 0.05). During follow-up, T790M resistance mutation was detected in 53 % of patients. Total and mutated EGFR analysis in cfDNA seems a relevant tool to characterize the molecular profile and prognosis of NSCLC patients harboring EGFR mutations.

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Growth inhibitory effect of rapamycin in Hodgkin-lymphoma cell lines characterized by constitutive NOTCH1 activation

Abstract

Growing evidence suggests that deregulation of signalling elements of Notch and mammalian target of rapamycin (mTOR) pathways contribute to tumorigenesis. These signals play important roles in cellular functions and malignancies. Their tumorigenic role in T-cell acute lymphoblastic leukaemia (T-ALL) is well known; however, their potential interactions and functions are poorly characterized in Hodgkin lymphoma (HL). The aim of our study was to characterize mTOR and Notch signalling elements in HL cell lines (DEV, L1236, KMH2) and human biopsies and to investigate their cross-talk in the tumorous process. High mTOR activity and constitutive NOTCH1 activation was confirmed in HL cell lines, without any known oncogenic mutations in key elements, including those common to both pathways. The anti-tumour effect of Notch inhibitors are well known from several preclinical models but resistance and side effects occur in many cases. Here, we tested mTOR and Notch inhibitors and their combinations in gamma-secretase inhibitor (GSI) resistant HL cells in vitro and in vivo. mTOR inhibitor alone or in combination was able to reduce tumour growth; furthermore, it was more effective in xenograft models in vivo. Based on these results, we suggest that constitutively activated NOTCH1 may be a potential target in HL therapy; furthermore, mTOR inhibitors may be effective for decreasing tumour growth if resistance to Notch inhibitors develop.

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Computer-based tools for assessing micro-longitudinal patterns of cognitive function in older adults

Abstract

Patterns of cognitive change over micro-longitudinal timescales (i.e., ranging from hours to days) are associated with a wide range of age-related health and functional outcomes. However, practical issues with conducting high-frequency assessments make investigations of micro-longitudinal cognition costly and burdensome to run. One way of addressing this is to develop cognitive assessments that can be performed by older adults, in their own homes, without a researcher being present. Here, we address the question of whether reliable and valid cognitive data can be collected over micro-longitudinal timescales using unsupervised cognitive tests.In study 1, 48 older adults completed two touchscreen cognitive tests, on three occasions, in controlled conditions, alongside a battery of standard tests of cognitive functions. In study 2, 40 older adults completed the same two computerized tasks on multiple occasions, over three separate week-long periods, in their own homes, without a researcher present. Here, the tasks were incorporated into a wider touchscreen system (Novel Assessment of Nutrition and Ageing (NANA)) developed to assess multiple domains of health and behavior. Standard tests of cognitive function were also administered prior to participants using the NANA system.Performance on the two "NANA" cognitive tasks showed convergent validity with, and similar levels of reliability to, the standard cognitive battery in both studies. Completion and accuracy rates were also very high. These results show that reliable and valid cognitive data can be collected from older adults using unsupervised computerized tests, thus affording new opportunities for the investigation of cognitive function.

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ASTRO APEx® and RO-ILS™ are applicable to medical malpractice in radiation oncology

Future Oncology Ahead of Print.


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Early discharge as a mediator of greater ICU-level care requirements in patients not enrolled on the AAML0531 clinical trial: a Children's Oncology Group report

Abstract

Previous data suggest that patients enrolled on clinical trials for treatment of cancer have better overall survival than patients who do not enroll; however, short-term outcomes relative to trial enrollment and corresponding mediators have not been assessed. A cohort of pediatric patients with newly-diagnosed acute myeloid leukemia was assembled from the Pediatric Health Information System. We evaluated whether patients not enrolled onto Children's Oncology Group trial AAML0531 had greater intensive care unit (ICU)-level requirements than enrolled patients and whether early discharge after chemotherapy administration mediated this association. Patients not enrolled on AAML0531 were more likely to be discharged early (aOR = 1.40, 95% confidence interval [CI]: 1.02, 1.90) and to require ICU-level care (aOR = 2.00, 95% CI: 1.06, 3.78) than enrolled patients, but early discharge explained only a small proportion (12.3%) of the absolute difference in ICU-level care risk. The direct effect of nonenrollment on the need for ICU-level care was significant (aOR = 1.89, 95% CI: 1.00, 3.94), whereas the indirect effect mediated through early discharge was not (aOR = 1.07, 95% CI: 0.95, 1.19). Factors other than postchemotherapy discharge strategy drive the difference in ICU utilization by trial enrollment status.

Patients not enrolled on AAML0531 were more likely to be discharged early (aOR = 1.40, 95% confidence interval [CI]: 1.02, 1.90) and to require intensive care unit (ICU)-level care (aOR = 2.00, 95% CI: 1.06, 3.78) than enrolled patients, but early discharge explained only a small proportion (12.3%) of the absolute difference in ICU-level care risk. The direct effect of nonenrollment on the need for ICU-level care was significant (aOR = 1.89, 95% CI: 1.00, 3.94), whereas the indirect effect mediated through early discharge was not (aOR = 1.07, 95% CI: 0.95, 1.19). Factors other than postchemotherapy discharge strategy drive the difference in ICU utilization by trial enrollment status.

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Fine-Tuning Cancer Immunotherapy through the Gut Microbiome

The equilibrium linking the intestinal microbiota, the intestinal epithelium, and the host immune system establishes host health and homeostasis, with perturbations of this balance resulting in chronic inflammatory and autoimmune immunopathologies. The mutualistic symbiosis between gut microbiota and host immunity raises the possibility that dysbiosis of the intestinal content also influences the outcome of cancer immunotherapy. Here, we present our recent findings that specific gut-resident bacteria determine the immunotherapeutic responses associated with CTLA-4 checkpoint blockade. This new evidence hints that interindividual differences in the microbiome may account for the significant heterogeneity in therapeutic and immunopathologic responses to immune checkpoint therapies. We discuss how this new understanding could improve the therapeutic coverage of immune checkpoint inhibitors, and potentially limit their immune-mediated toxicity, through the use of adjunctive "oncomicrobiotics" that indirectly promote beneficial immune responses through optimizing the gut microbiome. Cancer Res; 76(16); 1–6. ©2016 AACR.

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ASTRO APEx® and RO-ILS™ are applicable to medical malpractice in radiation oncology

Future Oncology Ahead of Print.


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Cancers, Vol. 8, Pages 72: Human Papillomavirus Genotype Distribution in Invasive Cervical Cancer in Pakistan

Few studies have assessed the burden of human papillomavirus (HPV) infection in Pakistan. We aim to provide specific information on HPV-type distribution in invasive cervical cancer (ICC) in the country. A total of 280 formalin-fixed paraffin-embedded tissue blocks were consecutively selected from Shaukat Khanum Memorial Cancer Hospital and Research Centre (Lahore, Pakistan). HPV-DNA was detected by SPF10 broad-spectrum PCR followed by DNA enzyme immunoassay and genotyping by LiPA25. HPV-DNA prevalence was 87.5% (95%CI: 83.0–91.1), with 96.1% of cases histologically classified as squamous cell carcinoma. Most of the HPV-DNA positive cases presented single infections (95.9%). HPV16 was the most common type followed by HPV18 and 45. Among HPV-DNA positive, a significantly higher contribution of HPV16/18 was detected in Pakistan (78.4%; 72.7–83.3), compared to Asia (71.6%; 69.9–73.4) and worldwide (70.8%; 69.9–71.8) and a lower contribution of HPVs31/33/45/52/58 (11.1%; 7.9–15.7 vs. 19.8%; 18.3–21.3 and 18.5%; 17.7–19.3). HPV18 or HPV45 positive ICC cases were significantly younger than cases infected by HPV16 (mean age: 43.3, 44.4, 50.5 years, respectively). A routine cervical cancer screening and HPV vaccination program does not yet exist in Pakistan; however, the country could benefit from national integrated efforts for cervical cancer prevention and control. Calculated estimations based on our results show that current HPV vaccine could potentially prevent new ICC cases.

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Altered tryptophan metabolism in human meningioma

Abstract

Meningiomas are the neoplasms that arise from the arachnoid cells of the meninges. It was reported that cancer cells escape from immune system through the metabolism of an aromatic essential amino acid tryptophan (TRP) via Kynurenine (KYN) pathway. However, the role of TRP metabolites such as, 5-Hydroxy tryptophan (5-HTP), 5-Hydroxy tryptamine (5-HT), N-acetyl serotonin (NAS), Melatonin (MEL), KYN, N-acetyl tryptamine, 5-Hydroxy indole acetic acid (5-HIAA) and 5-Methoxy indole acetic acid is not yet evaluated in human meningioma. Therefore, in the current study we have evaluated the levels of TRP and its metabolites in the progression of human meningioma using tumor biopsy samples and autopsy control meninges with Reverse Phase-HPLC. We here report that TRP metabolism favors towards KYN pathway in human meningioma and it could be due to increased indoleamine 2,3-dioxygenase 2 levels as we found its m-RNA levels to be up regulated in human meningioma. We observed significant increase in KYN and 5HIAA levels and significant decrease in TRP, 5-HTP, 5-HT, NAS and MEL levels in meningioma compared to control meninges. Since TRP metabolites regulate inducible nitric oxide synthase (INOS) gene expression and thereby nitric oxide (NO) production, we have also evaluated the INOS and NO levels. The INOS and NO levels were up regulated in human meningioma. The present data corroborates with existing data on TRP metabolism in tumor progression and may serve to target TRP metabolism as a therapeutic intervention.

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Relationship between weight loss and parameters of skeletal muscle function in patients with advanced cancer and fatigue

Abstract

Purpose

This study aims to determine the influence of significant weight loss on parameters of skeletal muscle function in a population of advanced cancer patients with fatigue.

Methods

A cross-sectional and comparative study was designed between two arms of advanced cancer patients with fatigue (fatigue numeral scale (FNS) ≥4). A arm (n = 27) with ≥5 % weight loss in the last 6 months, and B arm (n = 22) without weight loss. Muscle strength was examined by hand grip technique and measurements of body composition by bioimpedance analysis (BIA), values of hemoglobin, albumin, lactic dehydrogenase (LDH), c-reactive protein (CRP), urine creatinine, and FNS. These variables were compared between both groups and correlated within each group.

Results

here were no differences concerning parameters of muscle strength between both arms. A arm had values of CRP ≥10 ug/dl in 77 % compared with 38.5 % of B arm (p = 0.004). A arm showed a higher percentage of body cell mass (%BCM) than B arm (p = 0.005). The A arm also showed a lower percentage of fat mass (%FM) (p = 0.014) when compared to the B arm. FNS was higher in A arm (median 7 vs 5; p = 0.047). All the variables of muscle strength had a significant positive correlation. In A arm, BCM had a negative significant correlation with CRP (p = 0.021).

Conclusions

In this study, significant weight loss and high CRP did not have influence on parameters of skeletal muscular function. We consider that further studies should be necessary, preferably with longitudinal designs to evaluate these findings.

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How far along the disease trajectory? An examination of the time-related patient characteristics in the palliative oncology literature

Abstract

Purpose

Adequate reporting of time-related patient characteristics is needed for research findings to be properly interpreted, applied, and reproduced. Our objective was to characterize the time-related patient characteristics in palliative oncology studies and to examine the differences in time-related patient characteristics by various study characteristics.

Methods

We extracted time-related patient characteristics including actual survival, performance status, cancer stage, disease trajectory, study setting, and eligibility criteria (life expectancy and performance status) from an established cohort of original palliative oncology articles published in 2004 and 2009.

Results

Among 742 original articles, 409 (55 %) were case series. Only 247 (33 %) articles reported actual survival, 157 (21 %) reported actual performance status, 362 (49 %) cancer stage, and 392 (53 %) reported study setting. Based on all the available time-related characteristics, we were able to classify the studies into specific time-related categories in 378 (51 %) studies. Among these, only 47 (13 %) focused on patients in the last month of life. Compared to studies involving patients earlier in the disease trajectory, these studies were more likely to be case series (81 vs. 56 %, P = 0.005), retrospective (64 vs. 49 %, P = 0.03), and had a smaller sample size (median 20 vs. 61, P = 0.06).

Conclusions

A majority of studies did not adequately report time-related patient characteristics. We also identified a gap in both the quantity and quality of studies involving patients in the last month of life. Our study has implications for study reporting and future directions for palliative oncology research.

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“Enjoy glass of wine before eating:” a randomized trial to test the orexigenic effects of this advice in advanced cancer patients

Abstract

Background

Because the extant literature suggests wine increases appetite, this study sought to determine whether this effect could be observed in advanced cancer patients with appetite loss.

Methods

Advanced cancer patients with self-reported loss of appetite were randomly assigned to white wine with ≤15 % alcohol content twice a day for 3–4 weeks versus a nutritional supplement, such as Boost® or Ensure®. Patients assigned to wine were encouraged to also take a nutritional supplement, whereas patients assigned to the nutritional supplement arm were told to abstain completely from alcohol. Patient-reported outcomes were captured with a validated questionnaire to assess the primary endpoint of appetite improvement.

Results

A total of 141 patients (118 evaluable) were enrolled. Twenty-eight patients (48 %) in the wine arm reported an improvement in appetite at some point during the treatment period, whereas 22 patients (37 %) assigned to the nutritional supplement arm also reported improvement (p = 0.35). Other appetite-related questions and questionnaire items showed no statistically significant differences between treatment arms. In both arms, approximately 9 % of patients achieved weight stability (p = 0.98); median survival was not statistically different. Both interventions were well tolerated.

Conclusion

As prescribed in this trial, wine does not improve appetite or weight in advanced cancer patients.

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Oncologists’ experiences of discussing complementary and alternative treatment options with their cancer patients. A qualitative analysis

Abstract

Purpose

The rising use of complementary and alternative medicine (CAM) means oncologists are increasingly asked by patients to discuss CAM treatment options. However, no formal training or established standards are available on the subject. The aim of this paper was to investigate real-world discussions of CAM treatments. In particular, we wanted to learn about the values, norms and defining features that characterise oncologist-patient discussions on CAM.

Methods

Semi-standardised interviews with 17 oncologists were analysed using interpretation pattern analysis combined with thematic analysis.

Results

Advice on CAM is seen by oncologists as an important service they provide to their patients, even though their knowledge of the subject is often limited. Many interviewees mentioned an apparent lack of scientific proof, especially when their aim was to warn patients against the use of CAM. Discussions on CAM tend to reflect the idea that CAM belongs 'to another world', and judging by the interviews with oncologists, this notion appears to be shared by patients and oncologists alike.

Conclusions

Oncologists require reliable information on CAM and would profit from training in the communication of CAM treatment options to patients. Knowing scientific data on CAM would also lower barriers stemming from the view that CAM belongs 'to another world'. Under- and postgraduate education programmes should include training on how to respond to requests addressing possible CAM options.

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Cancer-related fatigue: appraising evidence-based guidelines for screening, assessment and management

Abstract

Purpose

There is inconsistent management of cancer-related fatigue (CRF) by health professionals worldwide. This research aims to identify the most appropriate guidelines for the management of cancer-related fatigue.

Methods

A systematic search of international literature identified evidence-based clinical practice guidelines for CRF. Four reviewers independently appraised the highest quality guidelines using the AGREE-II instrument and National Heath and Medical Research Council (NHMRC) guideline standards.

Results

Five guidelines met the inclusion criteria. Of these, the 2015 Canadian Association of Psychosocial Oncology (CAPO) CRF guidelines and the 2014 American Society of Clinical Oncology (ASCO) fatigue guidelines for cancer survivors were selected for in-depth appraisal. The CAPO guideline scored higher than the ASCO for five domains of the AGREE-II. For one domain, the differences were statistically significant (p ≤ 0.05). The CAPO guideline met 37 of 47 NHMRC mandatory guideline standards and the ASCO guideline met 20. The difference in the proportion of standards met was statistically significant for one domain (p ≤ 0.05). Both guidelines had low scores for applicability and implementation.

Conclusions

Currently, the CAPO guideline for cancer-related fatigue has the strongest evidence for use. To enhance implementation, further strategies for guideline dissemination and application are needed.

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Agreement between personally generated areas of quality of life concern and standard outcome measures in people with advanced cancer

Abstract

Purpose

People with advanced cancer experience different sequelae which have unique effects on quality of life (QOL). The patient-generated index (PGI) is a personalized measure that allows patients to nominate, rate, and value areas that have the most impact on QOL. Fatigue, pain, and aspects of physical function are among the top 10 areas with QOL impact. An area of validation that is lacking for the PGI is the extent to which spontaneously nominated areas of QOL that patients are concerned with, agree with ratings obtained from standard patient reported outcomes (PROs).

Methods

Data from 192 patients were used to compare ratings on fatigue, pain, and physical function obtained from PGI to those from standard outcome measures.

Results

Within one severity rating, agreement ranged from 32.1 to 76.9 % within the fatigue domain, 34.2 to 95.24 % for pain, and between 84.2 and 94.7 % for physical function. Of the 10 items where the PGI had the highest agreement, 7 came from the RAND-36. At the domain level, people nominating an area scored in the more impaired range on standard measures than people who did not.

Conclusion

PGI gives comparable information as do standard measures.

Implications for cancer

PGI provides important information to guide clinical care of the patient and also produces a legitimate total score suitable for research.

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Depressive symptoms in older long-term colorectal cancer survivors: a population-based analysis using the SEER-Medicare healthcare outcomes survey

Abstract

Purpose

Colorectal cancer survivorship has improved significantly over the last 20 years; however, few studies have evaluated depression among older colorectal cancer survivors, especially using a population-based sample. The aim of this study was to identify correlates for positive depression screen among colorectal cancer survivors who underwent potentially curative surgery.

Methods

Using the 1998–2007 Surveillance, Epidemiology, and End-Result registry and the Medicare Health Outcome Survey linked dataset, we identified patients over 65 with pathology confirmed and resected colorectal cancer enrolled in Medicare. Using univariate and multiple variable analyses, we identified characteristics of patients with and without positive depression screen.

Results

Resected colorectal cancer patients (1785) (median age 77, 50.8 % female) were identified in the dataset with 278 (15.6 %) screening positive for symptoms of depression. Median time from diagnosis to survey was 62 months. On univariate analysis, larger tumor size, advanced cancer stage, and extent of resection were not correlates of depressive symptoms (all p > 0.05). After adjusting for confounders, income less than US$30,000 per year (OR 1.50, 1.02–2.22, 95 % CI, p = 0.042), non-white race (OR 1.51, 1.05–2.17, 95 % CI, p = 0.027), two or more comorbidities (OR 1.78, 1.25–2.52, 95 % CI, p = 0.001), and impairment in activities of daily living (OR 5.28, 3.67–7.60, 95 % CI, p < 0.001) were identified as independent correlates of depressive symptoms in colorectal cancer survivors.

Conclusions

In the current study, socioeconomic status and features of physical health rather than tumor characteristics were associated with symptoms of depression among long-term colorectal cancer survivors.

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A systematic review of patient-reported outcome measures of neuropathy in children, adolescents and young adults

Abstract

Purpose

Peripheral neuropathy is an important, yet poorly studied, side effect of pediatric cancer treatment. There are many measures of patient-reported peripheral neuropathy in adults but very few in children. We aimed to systematically review and summarize reliable and valid patient-reported peripheral neuropathy scales used in pediatrics.

Methods

Four major electronic databases (Medline, Embase, EBSCO Host in Cumulative Index to Nursing and Allied Health Literature, and PsycINFO) were reviewed for studies that measured peripheral neuropathy in pediatric patients. Studies eligible for inclusion were those that described use of any patient-reported scale of peripheral neuropathy among children, adolescents, and young adults with any underlying diagnosis (not limited to cancer).

Results

From a total of 765 articles retrieved, 5 met eligibility criteria and were included. One was a neuropathy symptom score used in patients with diabetes, and the remaining four were in oncology patients and all were based on the total neuropathy score. All involved objective assessments conducted by trained professionals; none relied purely on patient report.

Conclusions

There are no validated instruments that consist solely of a patient-reported outcome measure of neuropathy in pediatrics and adolescents. Because the clinical evaluation of neuropathy requires specialized training, it is not generalizable in large studies conducted in many diverse institutions. Future studies should validate adult patient-reported neuropathy scales in pediatric and adolescent populations, or develop novel instruments designed for this population.

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Scalp cooling: a qualitative study to assess the perceptions and experiences of Australian patients with breast cancer

Abstract

Purpose

Chemotherapy-induced hair loss is a common and distressing side effect. Scalp cooling is increasingly being used to reduce this hair loss. The purpose of this study was to explore patients' perceptions and experience of scalp cooling.

Methods

Seventeen Australian women with a diagnosis of breast cancer participated in a focus group (n = 4) or a semi-structured interview (n = 3). Both scalp-cooled and non-scalp-cooled participant views were sought. Participant perceptions and experiences of scalp cooling were discussed as part of patients' overall chemotherapy experience and a thematic analysis conducted.

Results

Five themes emerged from the data: (1) scalp cooling in the context of treatment decision-making discussions, (2) hair loss expectations vs. experiences, (3) treatment-related expectations vs. experiences, (4) the promise of faster regrowth and (5) satisfaction with scalp cooling and future scalp cooling decision-making considerations. Information during treatment decision-making was the primary factor that influenced whether patient expectations were met. Faster regrowth was a motivator to continue treatment. Efficacy and tolerability of scalp cooling influenced future hypothetical treatment decision-making for both scalp-cooled and non-scalp-cooled participants.

Conclusions

This study provides the first in-depth exploration of patient attitudes to scalp cooling. The results highlight a need for accurate information regarding efficacy and tolerability as well as hair care information to assist patients with their treatment decision-making.

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Control of nausea with palonosetron versus granisetron, both combined with dexamethasone, in patients receiving cisplatin- or anthracycline plus cyclophosphamide-based regimens

Abstract

Purpose

In a comparative phase 3 study involving 1114 Japanese patients receiving highly emetogenic chemotherapy (HEC), palonosetron (PALO) was found to be superior to granisetron (GRA) for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in the delayed phase. This post hoc analysis of the phase 3 study evaluated the efficacy of PALO for the control of nausea.

Methods

The proportion of patients without nausea was assessed at 24-h intervals during the acute phase (0–24 h), delayed phase (24–120 h), and overall (0–120 h). No nausea rates were also evaluated by sex, type of chemotherapy (cisplatin or doxorubicin/epirubicin plus cyclophosphamide [AC/EC]), and age (<55 vs. ≥55 years). Nausea severity was categorized using a 4-point Likert scale (0 = no nausea to 3 = severe nausea).

Results

The proportion of patients without nausea was significantly higher in the PALO arm than in the GRA arm in the delayed phase (37.8 % vs. 27.2 %; p = 0.002) and overall (31.9 % vs. 25.0 %; p = 0.0117). When analyzed by stratification factors, the proportion of patients without nausea was significantly higher in the PALO arm in the delayed phase and overall in patients who were female, younger, or treated with cisplatin and in the delayed phase in patients who were older or treated with doxorubicin or epirubicin plus cyclophosphamide (all p < 0.05).

Conclusions

PALO was more effective than GRA in prophylaxis of HEC-induced nausea in the delayed phase and overall. In addition, PALO was more effective than GRA in young and female patients, who are at high risk of CINV, both in the delayed phase and overall.

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“Same-Day” administration of pegfilgrastim following myelosuppressive chemotherapy: clinical practice and provider rationale

Abstract

Purpose

To describe patient- and practice-related factors that physicians report affect their clinical decision to administer prophylactic pegfilgrastim to patients <24 h after completion of a myelosuppressive chemotherapy cycle (i.e., "same-day" pegfilgrastim).

Methods

Oncologists, hematologists, and hematologist-oncologists enrolled in a US national physician panel were invited to participate in a cross-sectional, web-based survey to assess physicians' reasons for prescribing "same-day" pegfilgrastim. Physicians were screened as eligible if they reported prescribing "same-day" pegfilgrastim within the previous 6 months. The survey assessed physician perspectives and physician-perceived patient/caregiver preferences.

Results

Of 17,478 invited physicians, 386 answered the screening questions; 151 (39.1 %) were eligible, agreed to participate, and completed the survey. Physicians estimated that overall 41.3 % of their patients treated with myelosuppressive chemotherapy received pegfilgrastim and that 31.6 % treated with pegfilgrastim received it on a "same-day" schedule. Approximately 36 % of physicians relied primarily on their clinical judgment when deciding to administer "same-day" pegfilgrastim. The clinical consideration reported most commonly by physicians as moderately or very important when deciding to administer "same-day" pegfilgrastim was previous febrile neutropenia (77.6 %). The most important patient-related consideration in the decision to administer "same-day" pegfilgrastim was patient/caregiver travel distance, and the most important practice-related consideration was the burden to the physician's practice of "next-day" administration (vs. same-day), reported by 84.7 % and 65.1 % of physicians as moderately or very important, respectively.

Conclusions

While clinical judgment, patients' risk factors, and practice burden were principal influences favoring "same-day" pegfilgrastim administration, physician-perceived patient preferences and logistical barriers also have important roles in this decision.

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“An addendum to breast cancer”: the triple negative experience

Abstract

Purpose

The triple negative breast cancer (TNBC) subtype, known to be aggressive with high recurrence and mortality rates, disproportionately affects African-Americans, young women, and BRCA1 carriers. TNBC does not respond to hormonal or biologic agents, limiting treatment options. The unique characteristics of the disease and the populations disproportionately affected indicate a need to examine the responses of this group. No known studies describe the psychosocial experiences of women with TNBC. The purpose of this study is to begin to fill that gap and to explore participants' psychosocial needs.

Method

An interpretive descriptive qualitative approach was used with in-depth interviews. A purposive sample of adult women with TNBC was recruited. Dominant themes were extracted through iterative and constant comparative analysis.

Results

Of the 22 participants, nearly half were women of color, and the majority was under the age of 60 years and within 5 years of diagnosis. The central theme was a perception of TNBC as "an addendum" to breast cancer. There were four subthemes: TNBC is Different: "Bottom line, it's not good"; Feeling Insecure: "Flying without a net"; Decision-Making and Understanding: "A steep learning curve"; and Looking Back: "Coulda, shoulda, woulda." Participants expressed a need for support in managing intense uncertainty with a TNBC diagnosis and in decision-making.

Conclusions

Women with all subtypes of breast cancer have typically been studied together. This is the first study on the psychosocial needs specifically of women with TNBC. The findings suggest that women with TNBC may have unique experiences and unmet psychosocial needs.

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Fall-risk prediction in older adults with cancer: an unmet need

Abstract

Falls in older adults with cancer are more common than in noncancer controls, yet no fall-risk screening tool has been validated in this population. We undertook a cross-sectional pilot study of the Falls Risk Questionnaire (FRQ) in 21 adults aged ≥65 receiving systemic cancer therapy. Participants completed the FRQ, geriatric assessment measures, and a measure of fear-of-falling. The recruitment rate was 87.5 %, with 95.2 % completion of the FRQ and additional geriatric assessment and quality of life measures. The FRQ correlated significantly with the Timed Up and Go test (Pearson r 0.479, p = 0.028). In addition, the FRQ score correlated directly with fear-of-falling and inversely with QOL, particularly physical health and neurotoxicity subscales. In conclusion, the FRQ was feasible in older adults receiving cancer therapy and correlates with measures of physical performance, functional status, and fear-of-falling. The FRQ may prove to be a valuable fall-risk screening tool to implement fall-prevention interventions in this vulnerable population of older adults with cancer.

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Health-related quality of life in patients with neuroendocrine tumors: an investigation of treatment type, disease status, and symptom burden

Abstract

Introduction

Neuroendocrine tumors (NETs) are malignant solid tumors arising in hormone-secreting tissue. They have historically been very difficult to treat, and advanced NETs are considered incurable. Surgery is the only potentially curative treatment option, though research is ongoing, investigating the efficacy of targeted therapies combined with more traditional chemotherapies. Frequent bowel movements and episodes of flushing are the most common symptoms.

Methods

The present study reports data from an anonymous patient survey of 663 eligible NET patients, identified with the assistance of patient advocacy groups. This study investigated the impact of treatment (surgery alone; surgery plus somatostatin analogue; other treatments) on quality of life (QOL). Finally, we investigate whether recurrent disease results in poorer QOL compared to disease treated curatively with surgery and remaining in remission.

Results and discussion

Results suggest that increased frequency of bowel movements and presence of any flushing symptoms are correlated with decreased quality of life. Treatment groups differed on most Patient Reported Outcomes Measurement Information System (PROMIS) global health and PROMIS-29 scores, including physical function, fatigue, pain, social function, and general physical and mental health, with the surgery group reporting significantly better scores than the other groups (effect size of differences ranged from 0.28 to 0.54). This may be possibly due to effective symptom control reached for these patients through surgery alone. After adjustment for carcinoid syndrome, the association with the treatment group disappeared for all domains except physical functioning. In terms of disease status, patients with recurrent disease reported poorer physical, social, and mental functions. Depression scores were similar between groups; however, patients with recurrent disease reported significantly higher anxiety compared to those with no current NET. Physical functioning was even more markedly different between groups, with recurrent NET patients reporting significantly impaired overall physical function, impaired sleep, and significant fatigue compared to those with no current NET. To our knowledge, this is the first study to comprehensively examine the effect of treatment group, disease status, and symptom burden on the quality of life in NET patients in a large sample. Limitations and future research directions are discussed.

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Psychometric assessment of the Chinese version of the MASCC Antiemesis Tool (MAT) for measuring chemotherapy-induced nausea and vomiting

Abstract

Purpose

This paper aims to assess the psychometric properties of the Chinese version of the MASCC Antiemesis Tool (MAT) for measuring chemotherapy-induced nausea and vomiting (CINV).

Methods

This was a psychometric study using a panel of experts and a prospective observational design. Six experts were invited to identify the content validity and face validity of the MAT, and 115 cancer patients were then recruited from three provincial medical centers in Fuzhou, China. The MAT was self-completed by the patients on the first and the fifth day after receiving the most recent chemotherapy, and patients also rated daily the Index of Nausea, Vomiting, and Retching (INVR) during the first 5 days after chemotherapy. Content validity was measured by the index of the content validity (CVI). Construct validity was estimated by the contrasted groups approach. Concurrent validity was measured by exploring the correlations between the INVR and MAT scores. The reliability of the MAT was examined by Cronbach's alpha and item-to-total correlations.

Results

One hundred and eleven subjects returned the completed measures. High content validity was determined. Contrasted groups analysis clearly discriminated the differences on the CINV symptom experiences between different age and gender groups. Excellent concurrent validity was identified, with the Spearman's correlation coefficient between the MAT total score and the INVR overall total score of 0.94 (P < 0.001). Cronbach's alpha for the MAT was 0.73, and the item-to-total correlations ranged from 0.50 to 0.71.

Conclusions

The MAT Chinese version is a valid, reliable, and convenient instrument for measuring CINV in Chinese cancer patients.

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Socio-demographic and clinical variables associated with psychological distress 1 and 3 years after breast cancer diagnosis

Abstract

Purpose

A large group of women (20–30 %) report psychological distress shortly after breast cancer diagnosis, and some experience continued or increased symptoms over time. The aim of this study was to investigate socio-demographic and clinical variables associated with sustained psychological distress in this patient group.

Methods

Women with breast cancer (n = 833) completed self-report questionnaires regarding socio-demographic and clinical variables shortly after (T1) and 3 years after diagnosis (T2) while data on illness severity were collected from a quality register. The Hospital Anxiety and Depression Scale was used as a measure of psychological distress at both time points.

Results

The number of participants who reported elevated levels of anxiety was 231 (28 %) at T1 and 231 (28 %) at T2 while elevated depressive symptoms was reported by 119 (14 %) women at T1 and 92 (11 %) at T2. Despite non-significant differences in mean scores over time, 91 (15 %) participants reported increased anxiety symptoms and 47 (7 %) reported increased depressive symptoms. Poor financial situation, lack of social support, previous psychiatric treatment, and high levels of fatigue were associated with both anxiety and depressive symptoms. Reporting high levels of fatigue was the variable most strongly associated with increased psychological distress over time.

Conclusion

Most participants reported decreased psychological distress over time, but there were subgroups of women who experienced sustained or increased symptoms of anxiety or depression. Participants with poor financial status, previous psychological problems, or high levels of fatigue may be at increased risk of psychological distress. Such individuals may benefit most from psychosocial interventions.

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Bisphosphonate-related osteonecrosis of the jaw: a review of the potential efficacy of low-level laser therapy

Abstract

Osteonecrosis of the jaw (ONJ) resulting from administration of bisphosphonates (BP) or denosumab is a rare but severe complication in cancer patients. Complete remission depends on the stage of ONJ; it can be estimated in the range of 20–30 %. Low-level laser therapy (LLLT) is a logical additional option, as it has been recognized effective for the management of chemotherapy and/or radiotherapy-induced mucositis. LLLT irradiation has anti-inflammatory actions and thus can help to control pain, as well as biostimulating properties with favorable actions on bacterial control and wound healing. We review the results of seven published studies of LLLT in BP-associated ONJ. LLLT results in an overall response rate of 55 % superior to that observed in controls (30 %). Our review suggests that there might be an advantage to add LLLT to the "classical" management of ONJ. This therapy is easy to administer and is not associated with any known side effects. Further research is needed to remove any doubt of protection or enhancement of carcinogenic processes. We believe that prospective well-controlled studies of LLLT in ONJ are warranted. If the positive results are confirmed, it would represent a great improvement for the quality of life of many patients.

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Hyponatremia in solid-tumor cancer patients: uncertainty regarding the use of vaptans

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Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF) is a valid screening tool in chemotherapy outpatients

Abstract

Purpose

In the oncology population where malnutrition prevalence is high, more descriptive screening tools can provide further information to assist triaging and capture acute change. The Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF) is a component of a nutritional assessment tool which could be used for descriptive nutrition screening. The purpose of this study was to conduct a secondary analysis of nutrition screening and assessment data to identify the most relevant information contributing to the PG-SGA SF to identify malnutrition risk with high sensitivity and specificity.

Methods

This was an observational, cross-sectional study of 300 consecutive adult patients receiving ambulatory anti-cancer treatment at an Australian tertiary hospital. Anthropometric and patient descriptive data were collected. The scored PG-SGA generated a score for nutritional risk (PG-SGA SF) and a global rating for nutrition status. Receiver operating characteristic curves (ROC) were generated to determine optimal cut-off scores for combinations of the PG-SGA SF boxes with the greatest sensitivity and specificity for predicting malnutrition according to scored PG-SGA global rating.

Results

The additive scores of boxes 1–3 had the highest sensitivity (90.2 %) while maintaining satisfactory specificity (67.5 %) and demonstrating high diagnostic value (AUC = 0.85, 95 % CI = 0.81–0.89). The inclusion of box 4 (PG-SGA SF) did not add further value as a screening tool (AUC = 0.85, 95 % CI = 0.80–0.89; sensitivity 80.4 %; specificity 72.3 %).

Conclusions

The validity of the PG-SGA SF in chemotherapy outpatients was confirmed. The present study however demonstrated that the functional capacity question (box 4) does not improve the overall discriminatory value of the PG-SGA SF.

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EGFR inhibitor-induced skin reactions: differentiating acneiform rash from superimposed bacterial infections

Abstract

Purpose

Epidermal growth factor receptor (EGFR) inhibitors are approved for use as targeted chemotherapeutic agents against multiple solid-organ malignancies. The most common side effect associated with EGFR inhibitor therapy is a papulopustular eruption, which can easily be confused with bacterial folliculitis. In this study, we examine the relative timing and location of the EGFR-induced papulopustular eruption compared to the associated bacterial superinfections.

Methods

In this retrospective chart review, patients enrolled in our institution's IRB-approved prospective registry of cutaneous reactions to chemotherapy were screened for inclusion. All patients who received an EGFR inhibitor and developed either a papulopustular eruption or bacterial superinfection at some point during treatment were included.

Results

Of the 157 patients who met inclusion criteria, 36 (23 %) developed bacterial superinfections at some point during EGFR therapy. Papulopustular eruptions developed in a highly predictable time course, with a mean time to onset of 1.5 weeks and mean duration of 9.4 weeks. Bacterial superinfections occurred at widely variable time points during therapy with a mean time to onset of 27.7 weeks. Papulopustular eruptions much more frequently affected the face (97 %), chest (75 %), and back (61 %), while bacterial superinfections occurred more commonly on the upper extremity (64 %), lower extremity (47 %), and abdomen (39 %).

Conclusions

The EGFR inhibitor-induced papulopustular eruption has a stereotypical time course and occurs in a characteristic distribution affecting the central face, upper chest, and back. Bacterial superinfections more frequently affect the extremities, abdomen, and groin and may occur at any point during EGFR therapy.

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Adjuvant Pelvic Radiation Therapy±Vaginal Brachytherapy in Patients With High-risk Stage I or Stage II Uterine Papillary Serous, Clear Cell, and High-grade Endometrioid Carcinoma

Purpose: Radiation therapy (RT) for stages I-II uterine papillary serous carcinoma (UPSC), clear cell (CC), and high-grade endometrioid (HGE) carcinoma present a treatment challenge. Regimens include external beam radiotherapy (EBRT) with or without brachytherapy. We examine the use of these radiation modalities in these endometrial cancers (EC) with respect to cause-specific survival (CSS). Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients with AJCC stages I-II UPSC, CC, or HGE cancer treated with hysterectomy and RT between 1998 and 2008. Patients who did not receive adjuvant RT or received brachytherapy alone were excluded. CSS was evaluated by the Kaplan-Meier survival analysis and the log-rank test was used to compare CSS. Multivariate analysis was performed using the Cox proportional hazards regression model. Adjusted hazard ratios (HR) were calculated for risk of EC death. Results: There were 1653 patients included in this analysis. The overall 100-month CSS for the entire cohort was 81.0%. The 100-month CSS was 85.3% for EBRT alone and 86.5% for EBRT+brachytherapy (P=0.72). Stage IC/IIA/IIB patients had a greater risk of EC death compared with stage IA/IB patients (adjusted HR=2.39; P

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Stereotactic Body Radiotherapy (SBRT) Is as Yet of Unproven Benefit for Patients With Lung Metastases

No abstract available

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Randomized Phase II Trial of Irinotecan/Docetaxel or Irinotecan/Docetaxel Plus Cetuximab for Metastatic Pancreatic Cancer: An Eastern Cooperative Oncology Group Study

Objectives: The primary objective was to determine the response rate in patients with metastatic pancreatic cancer treated in first line with irinotecan/docetaxel combination (Arm A) or with irinotecan/docetaxel/cetuximab combination (Arm B). Secondary endpoints were progression-free survival (PFS), overall survival (OS), toxicity, and the rate of thromboembolic events with prophylactic enoxaparin sodium. Patients and Methods: Patients were eligible who had measurable, metastatic adenocarcinoma of the pancreas, and normal bilirubin. All patients received anticoagulation. Docetaxel (35 mg/m2) and irinotecan (50 mg/m2) were administered once a week for 4 weeks followed by 2 weeks rest (Arm A) alone or with the addition of cetuximab (Arm B). The primary endpoint was response rate. Results: A total of 87 eligible patients were enrolled and treated. Grade 3/4 toxicity was observed in 74% of patients in Arm A and 76% in Arm B. The principal grade 3/4 toxicity was diarrhea. Response rates were 4.5% in Arm A and 7% in Arm B. Median PFS and OS were 3.9 and 6.5 months in Arm A and 4.5 and 5.4 months in Arm B. Conclusions: Docetaxel/irinotecan combination is associated with considerable toxicity. Objective responses were infrequent and addition of cetuximab in an unselected population was not beneficial, but PFS and OS were comparable with those achieved with other regimens. Docetaxel/irinotecan therapy is active in metastatic pancreatic cancer.

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The Missing Pieces in Reporting of Randomized Controlled Trials of External Beam Radiation Therapy Dose Escalation for Prostate Cancer

Randomized controlled trials (RCTs) are the most rigorous way of determining whether a cause-effect relation exists between treatment and outcome and for assessing the cost-effectiveness of a treatment. For many patients, cancer is a chronic illness; RCTs evaluating treatments for indolent cancers must evolve to facilitate medical decision-making, as "concrete" patient outcomes (eg, survival) will likely be excellent independent of the intervention, and detecting a difference between trial arms may be impossible. In this commentary, we articulate 9 recommendations that we hope future clinical trialists and funding agencies (including those under the National Cancer Institute) will take into consideration when planning RCTs to help guide subsequent interpretation of results and clinical decision making, based on RCTs of external beam radiation therapy dose escalation for the most common indolent cancer in men, that is, prostate cancer. We recommend routinely reporting: (1) race; (2) medical comorbidities; (3) psychiatric comorbidities; (4) insurance status; (5) education; (6) marital status; (7) income; (8) sexual orientation; and (9) facility-related characteristics (eg, number of centers involved, type of facilities, yearly hospital volumes). We discuss how these factors independently affect patient outcomes and toxicities; future clinicians and governing organizations should consider this information to plan RCTs accordingly (to maximize patient accrual and total n), select appropriate endpoints (eg, toxicity, quality of life, sexual function), actively monitor RCTs, and report results so as to identify the optimal treatment among subpopulations.

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Prognostic Significance of Nodal Ratio in Patients Undergoing Adjuvant Chemoradiotherapy After Curative Resection for Ampullary Cancer

Objectives: To analyze the outcome of patients with ampullary cancer who had undergone curative surgery followed by adjuvant chemoradiotherapy and to identify the prognostic factors for these patients Methods: Between January 1991 and August 2006, 71 patients with ampullary cancer underwent curative resection followed by adjuvant radiotherapy. There were 38 males and 33 females, and median age was 56 years (range, 28 to 77 y). Postoperative radiotherapy was delivered to tumor bed and regional lymph nodes up to 40 to 50 Gy at 2 Gy/fraction; 67 patients also received intravenous 5-fluorouracil as a radiosensitizer. Median follow-up duration was 72 months for survivors. Results: There were 5 isolated locoregional recurrences, 20 isolated distant metastases, and 11 combined locoregional and distant relapses. The 5-year locoregional relapse-free and overall survival rates were 76.2% and 64.5%, respectively. On multivariate analysis, nodal ratio and histologic differentiation were significant prognostic factors for overall survival (P=0.0382 and 0.0331, respectively). Conclusions: Adjuvant chemoradiotherapy after curative resection can achieve a long-term survival rate in patients with ampullary cancer. Nodal ratio and histologic differentiation are independent prognostic factors for these patients.

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Outcomes Following Hypofractionated Stereotactic Radiotherapy in the Management of Brain Metastases

Objective: To evaluate the outcomes of patients treated with hypofractionated stereotactic radiotherapy (HSRT) for radiosensitive and radioresistant brain metastases. Methods: Between August 2006 and July 2013, a total of 56 lesions in 44 patients with brain metastases were treated with HSRT. Twenty-three (41.1%) lesions were radioresistant. Patients were treated to a total dose of 24 to 30 Gy in 3 to 5 fractions. Median planning target volume was 6.18 cm3. The primary endpoint for this study was local control with secondary endpoints of overall survival, distant failure, performance status, and treatment toxicity. Results: The median follow-up for all patients was 5 months (range, 0.4 to 58.3 mo). Six- and 12-month Kaplan-Meier estimates of local control for all lesions were 85.6% and 79.4%, respectively. Radioresistant tumors had a 6- and 12-month local control rate of 87.0%, whereas radiosensitive tumors had a 6- and 12-month local control rate of 82.5% and 72.2%, respectively (P=0.41). Six- and 12-month distant brain control rates were 56.8% and 46.9%, respectively. Overall survival was significantly associated with recursive partitioning analysis classes I, II, and III (P=0.0003) and graded prognostic assessment classes 2 to 3 and 1 to 1.5 (P=0.041). Conclusions: HSRT is a safe and feasible alternative to single-session stereotactic radiosurgery for brain metastases. No difference was observed in local control rates between radioresistant and radiosensitive tumors.

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A Phase II Study of Concurrent Chemoradiotherapy With Paclitaxel and Cisplatin for Inoperable Esophageal Squamous Cell Carcinoma

Objectives: A phase II study was performed to investigate the efficacy and the safety of a 3-week schedule of paclitaxel (PTX) plus cisplatin (DDP) combined with concurrent radiotherapy for esophageal squamous cell cancer. Patients and Methods: Patients with newly diagnosed esophageal squamous cell cancer who had histologic proof of local-regional carcinoma of the esophagus, a Karnofsky performance status of 80 or greater, and normal liver, renal, and bone marrow functions were enrolled in the phase II trial. Chemotherapy consisted of DDP (25 mg/m2/d) for 3 days plus PTX (175 mg/m2) given for 3 hours, every 3 weeks for 4 cycles. The total dose of concurrent radiation with 68.4 Gy/44 Fx (late course–accelerated radiotherapy) or 61.2 Gy/34 Fx (conventional radiotherapy) was given at the first day of chemotherapy. Results: Between July 2008 and November 2011, 76 patients were enrolled in this trial. The median age was 58 years (range, 37 to 74 y). The stages were stage II (21 patients), stage III (27 patients), and stage IV (28 patients). A total of 89.5% (68/76) and 63.2% (48/76) patients completed ≥2 cycles and all 4 cycles of chemotherapy, respectively. With the median follow-up of 36 months, the overall median survival time was 28.5 months and the progression-free survival time was 14.7 months. One- and 3-year survival rates were 75% and 41%, respectively. Neutropenia grade 3 and 4 occurred in 30.3% and 31.6% of the patients, respectively. Conclusions: Radiotherapy concurrent with a 3-week schedule of PTX and DDP resulted in an encouraging overall survival rate, but a relatively higher hematological toxicity.

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Overview of Current Treatment Options and Investigational Targeted Therapies for Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Patients with squamous cell carcinoma of the head and neck (SCCHN) typically present with locally advanced (LA) stage III or IV disease and are treated with combined-modality therapy with chemotherapy, radiotherapy, and surgery (if resectable). These aggressive, upfront treatment measures are often associated with substantial morbidity, and about half the patients develop locoregional or distant recurrences. Thus, new therapeutic strategies are needed that offer similar efficacy benefits with less toxicity. Current research is focused on selectively targeting signaling pathways involved in the proliferation and malignant transformation of SCCHN cells and the tumor microenvironment. For example, the ErbB receptor pathway has been implicated in the development and progression of SCCHN, and several agents targeting this pathway and downstream effectors are in various phases of clinical investigation. Cetuximab, a monoclonal antibody against epidermal growth factor receptor (EGFR), is the only currently approved targeted therapy for the treatment of LA SCCHN. Additional agents targeting EGFR and other ErbB family members, including monoclonal antibodies (eg, panitumumab, nimotuzumab) and small-molecule tyrosine kinase inhibitors (eg, erlotinib, afatinib, lapatinib) are being studied in LA SCCHN with varying results. Other treatment strategies for LA SCCHN include targeting downstream effectors of signaling and resistance mechanisms to EGFR inhibitors (eg, mammalian target of rapamycin, Src family, and Aurora kinase family). Data from ongoing and future clinical trials will continue to refine current treatment paradigms for LA SCCHN and provide new therapeutic options and potential predictive biomarkers to improve patient efficacy and safety and abrogate resistance.

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Prognostic Significance of Standardized Uptake Value of Lymph Nodes on Survival for Stage III Non-small Cell Lung Cancer Treated With Definitive Concurrent Chemoradiotherapy

Objectives: Definitive concurrent chemoradiotherapy is the standard treatment for stage III non–small cell lung cancer (NSCLC). Previous studies showed that the tumor size and its metabolic activity are predictors of treatment outcome. We investigated whether there are new metabolic prognostic factors of survival for stage III NSCLC after definitive concurrent chemoradiotherapy. Patients and Methods: A total of 57 consecutive patients treated with definitive concurrent chemoradiotherapy for their stage IIIA (n=22) and stage IIIB (n=35) (AJCC 7th edition) unresectable NSCLC were identified. A total of 43 (75.4%) patients had positron emission tomography with integrated computed tomography (PET-CT) scan performed at diagnosis that were subsequently reviewed and analyzed. Prognosticators of progression-free survival (PFS), distant metastasis-free survival (DMFS), and overall survival (OS) were analyzed. Results: The median PFS, DMFS, and OS were 14.1, 12.6, and 37.8 months, respectively, after a median follow-up of 41.5 months. PFS advantage was demonstrated in stage IIIA versus stage IIIB (median 38.6 vs. 13.5 mo, P=0.020), N-stage N0-N2 versus N3 (median 16.7 vs. 8.1 mo, P

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Radiation Therapy for the Management of Brain Metastases

Brain metastases are the most common malignant intracranial tumors and carry a poor prognosis. The management of brain metastases may include a variety of treatment modalities including surgical resection, radiation therapy, and/or systemic therapy. The traditional treatment for brain metastasis involved whole brain irradiation. However, improved systemic control of primary cancers has led to longer survival for some groups of patients and there is increasing need to consider the late effects of radiation to the entire brain. With advances in imaging and radiation treatment planning and delivery stereotactic radiosurgery has become more frequently utilized and may be delivered through Gamma Knife Stereotactic Radiosurgery or linear accelerator-based systems. Furthermore, experience in treating thousands of patients on clinical trials has led to diagnosis-specific prognostic assessment systems that help guide our approach to the management of this common clinical scenario. This review provides an overview of the literature supporting radiotherapy for brain metastasis and an update on current radiotherapeutic options that is tailored for the nonradiation oncologist.

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Adherence Patterns to National Comprehensive Cancer Network Guidelines for Referral of Women With Breast Cancer to Genetics Professionals

Objective: Genetic predisposition is responsible for 5% to 10% of breast cancer. The National Comprehensive Cancer Network (NCCN) established guidelines delineating appropriate candidates for genetic counseling. This study aims to determine referral patterns for genetic counseling in women who met such guidelines. Materials and Methods: Utilizing an institutional tumor registry, patients from an academic oncology program who met a subset of NCCN guidelines for genetic referrals between 2004 and 2010 were identified (breast cancer diagnosis ≤50 y without a known BRCA mutation). A retrospective chart review was conducted. Statistics were analyzed using SAS version 9.2. Results: A total of 314 patients were identified and 107 (34.1%) were referred for genetic counseling. Median age at diagnosis was younger for those referred versus not referred (43 and 46 y; P

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More Pitfalls Related to Next-generation Sequencing (NGS)

No abstract available

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The Influence of Age and Comorbidity on the Benefit of Adding Androgen Deprivation to Dose-escalated Radiation in Men With Intermediate-risk Prostate Cancer

Objective: Androgen deprivation therapy (ADT) can improve outcomes for men with intermediate-risk prostate cancer (IR-PrCa) receiving external-beam radiotherapy (EBRT). Older men and men with significant comorbidity may be more susceptible to the harms of ADT, therefore we aimed to determine whether these men benefit from ADT. Methods: The adult comorbidity evaluation-27 index categorized severity of comorbidity in 636 men treated for IR-PrCa with dose-escalated EBRT (>75 Gy). The cohort was dichotomized at median age of 70. Multivariate Cox proportional hazard analysis evaluated the association of ADT with failure-free survival (FFS) for each age and comorbidity subgroup. Results: A total of 48% of men were 70 years and above. After adjustment for tumor characteristics, the addition of ADT to EBRT was associated with improved FFS for both men below 70 years of age (adjusted hazard ratio [AHR] 0.44; 95% confidence interval [CI], 0.19-0.99; P=0.046) and men 70 years and above (AHR 0.23; 95% CI, 0.06-0.91; P=0.035). ADT improved FFS for men below 70 years who had no or mild comorbidity (AHR 0.25; 95% CI, 0.09-0.73; P=0.011) but not for men below 70 years who had moderate or severe comorbidity (AHR 1.62; 95% CI, 0.35-7.49; P=0.537). Similarly, in men 70 years and above, there was a trend for improved FFS with ADT in healthy men (AHR 0.10; 95% CI, 0.01-1.08; P=0.058) but not in men with moderate to severe comorbidity (AHR 0.38; 95% CI, 0.06-2.56; P=0.318). Conclusions: The addition of ADT to dose-escalated EBRT can improve outcomes for both younger and older men with IR-PrCa. This benefit was more pronounced in healthy men.

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Letter to the Editor regarding the paper by Sang-Hee Yoon et al., Bilateral salpingectomy can reduce the risk of ovarian cancer in the general population: A meta-analysis

Publication date: September 2016
Source:European Journal of Cancer, Volume 64
Author(s): Gabriela Palma-Ardiles, Wendy Hernandez-Fernandez, Ximena Gianuzzi, Adrian V. Hernandez




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Identification of a novel metabolic-related mutation (IDH1) in metastatic pancreatic cancer.

Identification of a novel metabolic-related mutation (IDH1) in metastatic pancreatic cancer.

Cancer Biol Ther. 2016 Jul 28;:0

Authors: Brody JR, Yabar CS, Zarei M, Bender J, Matrisian LM, Rahib L, Heartwell C, Mason K, Yeo CJ, Peiper SC, Jiang W, Varieur K, Madhavan S, Petricoin E, Fortuna D, Curtis M, Wang ZX, Pishvaian MJ, Winter JM

Abstract
Isocitrate dehydrogenase 1 (IDH1) is a metabolic enzyme implicated in cancer cell metabolic reprogramming. This is underscored by the detection of functional, somatic IDH1 mutations frequently found in secondary glioblastoma. To our knowledge, there has never been a reported, validated case of an IDH1 mutation in a pancreatic ductal adenocarcinoma (PDA). Herein, we present a case of a patient with metastatic PDA that harbored a potentially actionable, albeit rare, IDH1 mutation. As part of the Know Your Tumor project (Pancreatic Cancer Action Network), a 48-year-old female was diagnosed with metastatic PDA and subsequently started on standard of care chemotherapy, during which her hepatic lesions progressed. Detailed molecular profiling was performed on a biopsy from a liver lesion that demonstrated an IDH1 mutation, R132H. This mutation was confirmed by an independent sequencing reaction from the tumor sample, and by immunohistochemistry using an antibody specific for the IDH1 R132H mutation. The patient subsequently received a mutant IDH1 inhibitor (AG-120, Agios Pharmaceuticals, Cambridge, MA), but with no response. IDH1 mutations are common in certain cancer types, but have not been reported in PDA. We report the first case of an IDH1 mutation in this tumor type, perhaps providing a rare opportunity for a targeted therapy as a treatment option for PDA.

PMID: 27466707 [PubMed - as supplied by publisher]

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Identification of a novel metabolic-related mutation (IDH1) in metastatic pancreatic cancer.

Identification of a novel metabolic-related mutation (IDH1) in metastatic pancreatic cancer.

Cancer Biol Ther. 2016 Jul 28;:0

Authors: Brody JR, Yabar CS, Zarei M, Bender J, Matrisian LM, Rahib L, Heartwell C, Mason K, Yeo CJ, Peiper SC, Jiang W, Varieur K, Madhavan S, Petricoin E, Fortuna D, Curtis M, Wang ZX, Pishvaian MJ, Winter JM

Abstract
Isocitrate dehydrogenase 1 (IDH1) is a metabolic enzyme implicated in cancer cell metabolic reprogramming. This is underscored by the detection of functional, somatic IDH1 mutations frequently found in secondary glioblastoma. To our knowledge, there has never been a reported, validated case of an IDH1 mutation in a pancreatic ductal adenocarcinoma (PDA). Herein, we present a case of a patient with metastatic PDA that harbored a potentially actionable, albeit rare, IDH1 mutation. As part of the Know Your Tumor project (Pancreatic Cancer Action Network), a 48-year-old female was diagnosed with metastatic PDA and subsequently started on standard of care chemotherapy, during which her hepatic lesions progressed. Detailed molecular profiling was performed on a biopsy from a liver lesion that demonstrated an IDH1 mutation, R132H. This mutation was confirmed by an independent sequencing reaction from the tumor sample, and by immunohistochemistry using an antibody specific for the IDH1 R132H mutation. The patient subsequently received a mutant IDH1 inhibitor (AG-120, Agios Pharmaceuticals, Cambridge, MA), but with no response. IDH1 mutations are common in certain cancer types, but have not been reported in PDA. We report the first case of an IDH1 mutation in this tumor type, perhaps providing a rare opportunity for a targeted therapy as a treatment option for PDA.

PMID: 27466707 [PubMed - as supplied by publisher]

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Identification of a novel metabolic-related mutation (IDH1) in metastatic pancreatic cancer.

Identification of a novel metabolic-related mutation (IDH1) in metastatic pancreatic cancer.

Cancer Biol Ther. 2016 Jul 28;:0

Authors: Brody JR, Yabar CS, Zarei M, Bender J, Matrisian LM, Rahib L, Heartwell C, Mason K, Yeo CJ, Peiper SC, Jiang W, Varieur K, Madhavan S, Petricoin E, Fortuna D, Curtis M, Wang ZX, Pishvaian MJ, Winter JM

Abstract
Isocitrate dehydrogenase 1 (IDH1) is a metabolic enzyme implicated in cancer cell metabolic reprogramming. This is underscored by the detection of functional, somatic IDH1 mutations frequently found in secondary glioblastoma. To our knowledge, there has never been a reported, validated case of an IDH1 mutation in a pancreatic ductal adenocarcinoma (PDA). Herein, we present a case of a patient with metastatic PDA that harbored a potentially actionable, albeit rare, IDH1 mutation. As part of the Know Your Tumor project (Pancreatic Cancer Action Network), a 48-year-old female was diagnosed with metastatic PDA and subsequently started on standard of care chemotherapy, during which her hepatic lesions progressed. Detailed molecular profiling was performed on a biopsy from a liver lesion that demonstrated an IDH1 mutation, R132H. This mutation was confirmed by an independent sequencing reaction from the tumor sample, and by immunohistochemistry using an antibody specific for the IDH1 R132H mutation. The patient subsequently received a mutant IDH1 inhibitor (AG-120, Agios Pharmaceuticals, Cambridge, MA), but with no response. IDH1 mutations are common in certain cancer types, but have not been reported in PDA. We report the first case of an IDH1 mutation in this tumor type, perhaps providing a rare opportunity for a targeted therapy as a treatment option for PDA.

PMID: 27466707 [PubMed - as supplied by publisher]

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Social Network, Surgeon, and Media Influence on the Decision to Undergo Contralateral Prophylactic Mastectomy.

Objectives: The rate of contralateral prophylactic mastectomy (CPM) has risen sharply in the past decade. The current study was designed to examine social network, surgeon, and media influence on patients' CPM decision-making, examining not only who influenced the decision, and to what extent, but also the type of influence exerted. Methods: Patients (N=113) who underwent CPM at 4 Indiana University-affiliated hospitals between 2008 and 2012 completed structured telephone interviews in 2013. Questions addressed the involvement and influence of the social network (family, friends, and nonsurgeon health professionals), surgeon, and media on the CPM decision. Results: Spouses, children, family, friends, and health professionals were reported as exerting a meaningful degree of influence on patients' decisions, largely in ways that were positive or neutral toward CPM. Most surgeons were regarded as providing options rather than encouraging or discouraging CPM. Media influence was present, but limited. Conclusions: Patients who choose CPM do so with influence and support from members of their social networks. Reversing the increasing choice of CPM will require educating these influential others, which can be accomplished by encouraging patients to include them in clinical consultations, and by providing patients with educational materials that can be shared with their social networks. Surgeons need to be perceived as having an opinion, specifically that CPM should be reserved for those patients for whom it is medically indicated. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://ift.tt/1hexVwJ Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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In response: Can we rely on the adequate mesorectum excision and the complete pathological response in case of rectal signet-ring cell carcinoma

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Recurrent pleomorphic adenoma of the parotid gland: Institutional experience and review of the literature

Background

Recurrent pleomorphic adenoma (PA) of the parotid gland is a challenging surgical issue with controversy regarding management and long term outcome.

Methods

All patients who were operated for recurrent PA of the parotid gland between the years 1991 and 2013 were reviewed. Patient demographics, clinicopathologic variables, and operative details were collected retrospectively.

Results

A total of 22 patients were operated for recurrent PA of the parotid gland. Mean interval between recurrences was 7 and 6 years for first recurrence and second recurrence, accordingly. Second recurrence was significantly influenced by younger age at initial treatment (P = 0.009). Only two patients (9%) with a recurrence developed facial nerve paralysis following surgery. Adjuvant radiotherapy was given to nine patients with no evidence of disease progression or recurrence. There were no cases of malignant transformation.

Conclusions

Recurrent PA of the parotid gland tends to occur in long intervals in a multifocal pattern. Adjuvant radiotherapy could be suggested as an alternative for surgery. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

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Validation of clinical risk scores for laparoscopic liver resections of colorectal liver metastases: A 10-year observed follow-up study

Objective

The aim of this study was to validate clinical risk scores in patients underwent laparoscopic resection of colorectal liver metastases (CLM) with 5 years follow-up or more, and assess 5- and 10-year actual survival in this group.

Methods

A total of 516 laparoscopic liver resections were performed in 406 patients with CLM between February 1998 and September 2015. A follow-up of 5 and 10 years could be assessed in 144 and 29 patients, respectively. The Fong score, pre- and postoperative Basingstoke Predictive Index (BPI), Nordlinger score, and Iwatsuki score were validated.

Results

Five- and ten-year cancer-related actual survival was 54% and 32%, respectively. The Fong score, pre- and postoperative BPI and the Nordlinger score divided patients into risk groups with significant difference in survival between the groups. However, predicted 5-year survival rates were lower than the actual 5-year survival (mean difference in 17%,13%, 20%, and 30%, respectively).

Conclusion

The Fong score, pre- and postoperative BPI and the Nordlinger score systems can be used to predict survival for laparoscopically operated patients in the era of multimodal-treatment after adjusting of survival rates. The actual five- and 10-year survival after laparoscopic resection of CLM is similar to results previously published for open liver resection. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

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Solid pseudopapillary tumors of the pancreas: Specific pathological features predict the likelihood of postoperative recurrence

Background

Since their introduction in the WHO classification, the incidence of solid pseudopapillary tumors (SPTs) of the pancreas has progressively increased, mainly because of the widespread use of cross-sectional imaging. Few recent studies have analyzed the biological behavior of SPTs, but reliable data on long-term follow-up are needed.

Methods

Retrospective analysis of two Institutions with high caseload, The Department of General Surgery—Pancreas Institute, University of Verona Hospital Trust and the Department of General Surgery, Massachusetts General Hospital, Harvard Medical School, was carried out. Data from 131 consecutive resections for SPT performed during the last three decades were collected and analyzed.

Results

The majority of patients were female (86.3%) with a median age of 33 (7–68) years. The prevalent location was the pancreatic tail (33.5%). Applying the WHO criteria, 16 (12.2%) SPTs were considered malignant due to the presence of at least pancreatic parenchyma (9.9%), perineural (4.6%), and/or angiovascular invasion (2.3%). After a median of 62 months after surgery, only two patients had a recurrence (1.5%). Both of them fulfilled the WHO criteria for malignant SPT (vs. 10.7% of those who did not recur, P = 0.01), had an infiltrative growth pattern (vs. 10.8%, P = 0.01), pancreatic parenchyma invasion (vs. 9.7%, P = 0.01) and capsular invasion (vs. 4.9%, P = 0.004).

Conclusion

Overall, SPTs are associated with excellent survival results after surgical resection. Disease recurrence is extremely rare, and might occur if the primary tumor presents with either pancreatic parenchyma or capsule invasion. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

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