Prognostic factors affecting postoperative survival of patients with solitary small hepatocellular carcinoma

Small hepatocellular carcinoma (sHCC) is a unique variant of HCC that is characterized by small tumor size (maximum tumor diameter ≤3 cm) and favorable long-term outcomes. The present study aimed to define cli...

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Subtype distribution and long-term titer fluctuation patterns of serum anti-Epstein–Barr virus antibodies in a non-nasopharyngeal carcinoma population from an endemic area in South China: a cohort study

Serum immunoglobulin A antibodies against Epstein–Barr virus (EBV), viral capsid antigen (VCA-IgA) and early antigen (EA-IgA), are used to screen for nasopharyngeal carcinoma (NPC) in endemic areas. However, t...

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Clinical and molecular characteristics of East Asian patients with von Hippel–Lindau syndrome

Von Hippel–Lindau (VHL) syndrome is a dominantly inherited multisystem cancer syndrome caused by a heterozygous mutation in the VHL tumor suppressor gene. Previous studies suggested that similar populations of Ca...

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Prognostic factors affecting postoperative survival of patients with solitary small hepatocellular carcinoma

Abstract

Background

Small hepatocellular carcinoma (sHCC) is a unique variant of HCC that is characterized by small tumor size (maximum tumor diameter ≤3 cm) and favorable long-term outcomes. The present study aimed to define clinicopathologic factors that predict survival in patients with sHCC.

Methods

The study population consisted of 335 patients who underwent hepatectomy for solitary sHCC between December 1998 and 2010. Prognostic factors were evaluated using Kaplan–Meier curves and Cox proportional hazard models.

Results

The 5-year overall survival (OS) and recurrence-free survival (RFS) rates were 77.7% and 59.9%, respectively. Kaplan–Meier curves showed that tumor size and vascular invasion had prognostic significance within this relatively selected cohort (P < 0.05). Multivariate analysis confirmed that increased tumor size and vascular invasion were independent prognostic factors for short OS (hazard ratio [HR] = 2.367, 95% confidence interval [CI] 1.406–3.985; HR = 2.954, 95% CI 1.781–4.900) and RFS (HR = 1.779, 95% CI 1.259–2.514; HR = 1.699, 95% CI 1.165–2.477) in sHCC patients (P < 0.05). Importantly, a proposed prognostic scoring model was derived according to the two variables; tumor size and extent of vascular invasion were significantly associated with OS and RFS in patients with sHCC (P < 0.001).

Conclusions

Tumor size and vascular invasion are feasible and useful prognostic factors for sHCC. The proposed prognostic model, based on tumor size and vascular invasion, is informative in predicting survival in sHCC patients undergoing hepatectomy.

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Human papillomavirus genotypes distribution in cervical cancer cases in Gabon

Abstract

Background

Cervical cancer is a real public health problem in African countries. The relation between HPV and cervical cancer is well established. However, it is known that the distribution of HPV genotypes differ geographically and this may influence the effectiveness of the three available vaccines, which among other HPV genotypes targets the genotypes 16 and 18 that cause about 70 % of cervical cancers cases. The objective of this study was to identify for the first time the HPV genotypes distribution in cervical cancer specimens obtained from Gabonese women.

Methods

A total of 105 cervical samples including 93 formalin-fixed paraffin embedded tissues collected between 2007 and 2013 and 12 fresh biopsies collected in August 2013 were investigated. The presence of HPV DNA was analyzed by nested PCR with primers MY09/11 and GP5+/6+ followed by sequencing for HPV genotyping.

Results

Amplification of the housekeeping gene (β-globin) with PCO4/GH20 primers was successful for 91.4 % (96/105) of the cervical cancer samples and HPV DNA was detected in all the 96 samples. Five different HPV genotypes were identified. HPV 16 [58.3 %; 95 % IC: 48.44–68.16] was the most common genotype followed by HPV 33 [25.0 %; 95 % IC: 16.34–33.66], HPV 18 [8.4 %; 95 % IC: 2.86–13.94], HPV 70 [7.3 %; 95 % IC: 2.1–12.5] and HPV 31 [1.1 %; 95 % IC: −0.986–3.186]. HPV 16 was also the most prevalent in all histological malignant lesions. It was found in 56.6 % of squamous cervical carcinoma and 69.2 % of adenocarcinoma. Concerning the HPV positive adenocarcinoma cases, HPV 18 was identified in 7.7 % (1/13).

Conclusion

These findings show the predominance of HPV 16 in cervical cancer cases among Gabonese women. However, HPV33 is more prevalent than HPV18. Our study suggests that HPV vaccines may be effective at reducing the burden of cervical cancer in Gabon.

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Platelet–lymphocyte ratio is an independent prognostic factor in patients with ALK-positive non-small-cell lung cancer

Future Oncology Ahead of Print.


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Spinal metastases: multimodality imaging in diagnosis and stereotactic body radiation therapy planning

Future Oncology Ahead of Print.


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Brain tumors in Li-Fraumeni syndrome: a commentary and a case of a gliosarcoma patient

Future Oncology Ahead of Print.


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Risk of severe rash in cancer patients treated with EGFR tyrosine kinase inhibitors: a systematic review and meta-analysis

Future Oncology Ahead of Print.


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RSK as a Drug Target for TNBC

Metastatic breast cancer is an incurable disease and identification of novel therapeutic opportunities is vital. Triple negative breast cancer (TNBC) frequently metastasizes and high levels of activated RSK, a downstream MEK-ERK1/2 effector, are found in TNBC. We demonstrate using direct pharmacological and genetic inhibition of RSK1/2 that these kinases contribute to the TNBC metastatic process in vivo. Kinase profiling demonstrated that RSK1 and RSK2 are the predominant kinases targeted by the new inhibitor, which is based on the natural product, SL0101. Further evidence for selectivity was provided by the observations that silencing RSK1 and RSK2 eliminated the ability of the analogue to further inhibit survival or proliferation of a TNBC cell line. In vivo, the new derivative was as effective as the FDA-approved MEK inhibitor, trametinib, in reducing the establishment of metastatic foci. Importantly, inhibition of RSK1/2 did not result in activation of AKT, which is known to limit the efficacy of MEK inhibitors in the clinic. Our results demonstrate that RSK is a major contributor to the TNBC metastatic program and provide preclinical proof-of-concept for the efficacy of the novel SL0101 analogue in vivo.

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Optical Imaging of Breast Cancer Chemotherapy Response

The prospective multi-center ACRIN 6691 trial was designed to evaluate whether changes from baseline to mid-therapy in a Diffuse Optical Spectroscopic Imaging (DOSI)-derived imaging endpoint, the Tissue Optical Index (TOI), predict pathologic complete response (pCR) in women undergoing breast cancer neoadjuvant chemotherapy (NAC). DOSI instruments were constructed at the University of California, Irvine and delivered to 6 institutions where 60 subjects with newly-diagnosed breast tumors (at least 2 cm in the longest dimension) were enrolled over a 2-year period. Bedside DOSI images of the tissue concentrations of deoxy-hemoglobin (ctHHb), oxy-hemoglobin (ctHbO2), water (ctH2O), lipid, and TOI (ctHHb x ctH2O/lipid) were acquired on both breasts up to 4 times during NAC treatment: baseline, one-week, mid-point, and completion. Of the 34 subjects (mean age 48.4 {plus minus} 10.7 years) with complete, evaluable data from both normal and tumor-containing breast, 10 (29%) achieved pCR as determined by central pathology review. The percent change in tumor to normal TOI ratio (%TOITN) from baseline to mid-therapy ranged from -82% to 321%, with a median of -36%. Using pCR as the reference standard and receiver-operating characteristic curve methodology, %TOITN AUC was 0.60 (95% CI 0.39 to 0.81). In the cohort of 17 patients with baseline tumor oxygen saturation (%StO2) greater than the 77% population median, %TOITN AUC improved to 0.83 (95% CI 0.63 to 1.00). We conclude that the combination of baseline functional properties and dynamic optical response shows promise for clinical outcome prediction.

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CFHR1 and CFHR3 associate with anti-CD20 patient response

Purpose: Anti-CD20 monoclonal antibody (mAb) therapies, including rituximab and obinutuzumab (GA101) are common treatments for follicular lymphoma (FL). In an effort to better understand the role of complement in mAb action, we recently performed germline SNP profiling on 142 FL patients and found rs3766404 genotype correlated with patient response to rituximab. To assess the role of three SNP-associated complement regulatory proteins (CFH, CFHR1 and CFHR3) in clinical response to anti-CD20 mAb, we studied two cohorts of patients treated with anti-CD20 mAb. Experimental Design: Cohorts included the Iowa/Mayo Lymphoma SPORE observational cohort of subjects with a new diagnosis of FL treated with rituximab, and the GAUSS prospective randomized trial cohort of FL subjects randomized to receive single agent rituximab or obinutuzumab. Circulating protein expression was measured for CFH, CFHR1 and CFHR3 and correlated to clinical outcome. Results: rs3766404 genotype correlated with expression of the related downstream genes CFHR1 and CFHR3. Loss of CFHR1 expression correlated with inferior patient outcome in the observational cohort, but not in the GAUSS cohort. Loss of CFHR3 correlated with superior event-free survival in GAUSS subjects treated with obinutuzumab, but not rituximab. Conclusions: We conclude that the relationship between complement regulatory proteins CFHR1 and CFHR3 and response to anti-CD20 mAb therapy varies based on the specific anti-CD20 mAb used. We propose that CFHR3 is a candidate biomarker for obinutuzumab response. Further studies are needed to validate these findings and to better understand how complement pathways and complement regulatory proteins impact on the efficacy of anti-CD20 mAb therapy.

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Recurrent TRIO fusion in non-translocation-related sarcomas

Purpose:Despite various differences, non-translocation-related sarcomas (comprising UPS, LMS, MFS e.g.) are unified by their complex genetics. Extensive analysis of the tumor genome using molecular cytogenetic approaches showed many chromosomal gains, losses and translocations per cell. Genomic quantitative alterations and expression variations have been extensively studied by adapted high-throughput approaches, yet translocations still remained unscreened. We therefore analyzed 117 non-translocation-related sarcomas by RNA sequencing to identify fusion genes. Experimental Design:We performed RNA sequencing and applied a bioinformatics pipeline dedicated to detection of fusion transcripts. RT-PCR and Sanger sequencing were then applied to validate predictions and to search for recurrence and specificity. Results:Among the 6,772 predicted fusion genes, 420 were in-frame. One recurrent rearrangement, consistently involving TRIO with various partners, was identified in 5.1% of cases. TRIO translocations are either intra-chromosomal with TERT or inter-chromosomal with LINC01504 or ZNF558. Our results suggest that all translocations lead to a truncated TRIO protein either directly or indirectly by alternative splicing. TRIO rearrangement is associated with a modified transcriptomic program to immunity/inflammation, proliferation and migration and an increase in proliferation. Conclusions:TRIO fusions have been identified in four different sarcoma histotypes likely meaning that they are not related to a primary oncogenic event but rather to a secondary one implicated in tumor progression. Moreover, they appear to be specific to non-translocation-related sarcomas since no such rearrangement was identified in sarcomas with simple genetics. More cases could lead to a significant association of these fusions to a specific clinical behavior.

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The deficiency of galectin-3 in stromal cells leads to enhanced tumor growth and bone marrow metastasis

Abstract

Background

Galectin-3 is a multifunctional β-galactoside-binding lectin that once synthesized, is expressed in the nucleus, cytoplasm, cell surface and in the extracellular environment. Because of its unique structure, galectin-3 can oligomerize forming lattice upon binding to multivalent oligossacharides and influence several pathologic events such as tumorigenesis, invasion and metastasis.

Methods

In our study, balb/c Lgals3+/+ and Lgals3−/− female mice were inoculated in the fourth mammary fat pad with 4T1 breast cancer cell line. The primary tumor, inguinal lymph nodes and iliac bone marrow were evaluated 15, 21 and 28 days post-injection. The primary tumor growth was evaluated by measuring the external diameter, internal growth by ultrasound and weight of the excised tumor. The presence of cancer cells in the draining lymph nodes and iliac crest bone marrow were performed by immunohistochemistry, PCR and clonogenic metastatic assay.

Results

In this study we demonstrated that the deletion of galectin-3 in the host affected drastically the in vivo growth rate of 4T1 tumors. The primary tumors in Lgals3−/− mice displayed a higher proliferative rate (p < 0,05), an increased necrotic area (p < 0,01) and new blood vessels with a wider lumen in comparison with tumors from Lgals3+/+ mice (P < 0,05). Moreover, we detected a higher number of 4T1-derived metastatic colonies in the lymph nodes and the bone marrow of Lgals3−/− mice (p < 0,05). Additionally, healthy Lgals3−/− control mice presented an altered spatial distribution of CXCL12 in the bone marrow, which may explain at least in part the initial colonization of this organ in Lgals3−/− injected with 4T1 cells.

Conclusions

Taken together, our results demonstrate for the first time that the absence of galectin-3 in the host microenvironment favors the growth of the primary tumors, the metastatic spread to the inguinal lymph nodes and bone marrow colonization by metastatic 4T1 tumor cells.

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The usefulness of 18 F-FDG PET/CT for assessing methotrexate-associated lymphoproliferative disorder (MTX-LPD)

Abstract

Background

Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a benign lymphoid proliferation or malignant lymphoma in patients who have been treated with MTX. MTX withdrawal and observation for a short period should be considered in the initial management of patients who develop LPD while on MTX therapy. Here we evaluated the diagnostic accuracy and predictive value of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) for MTX-LPD.

Methods

We retrospectively investigated the cases of 15 patients clinically suspected of having MTX-LPD. A total of 324 anatomic regions (207 nodal and 117 extranodal regions) were assessed by ¹⁸F-FDG PET/CT and by multi-detector row CT (MDCT). Each anatomic region was classified as either malignant or benign. The uptake of ¹⁸F-FDG was assessed semi-quantitatively with the standardized uptake value maximum (SUVmax), the whole-body metabolic tumor volume (WBMTV), and the whole-body total lesion glycolysis (WBTLG) in order to investigate predictive factors of spontaneous regression after the withdrawal of MTX.

Results

MTX-LPD lesions were observed in 92/324 (28.4 %) regions. ¹⁸F-FDG PET/CT showed 90.2 % sensitivity, 97.4 % specificity, and 95.4 % accuracy, values which were significantly higher than those of MDCT (59.8, 94.8, and 84.9 %, respectively. p < 0.002). After the withdrawal of MTX, 9/15 patients (60.0 %) achieved complete response (CR). The SUVmax, WBMTV and WBTLG values of the CR patients were 9.2 (range 2.8–47.1), 44.3 (range 0–362.6) ml, 181.8 (range 0–2180.9) ml, respectively, which were not significantly different from those of the non-CR patients: 10.6 (range 0–24.9), 15.7 (range 0–250.1) ml, and 97.4 (range 0–1052.1) ml.

Conclusions

Although ¹⁸F-FDG PET/CT was a useful tool to detect MTX-LPD lesions, none of the ¹⁸F-FDG PET parameters before the withdrawal of MTX could be used to predict CR after the withdrawal of MTX.

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Goldilocks and margins for DCIS: Identifying “just right”

Publication date: Available online 15 August 2016
Source:Practical Radiation Oncology
Author(s): Reshma Jagsi




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FLASH protects ZEB1 from degradation and supports cancer cells' epithelial-to-mesenchymal transition

FLASH protects ZEB1 from degradation and supports cancer cells' epithelial-to-mesenchymal transition

Oncogenesis 5, e254 (August 2016). doi:10.1038/oncsis.2016.55

Authors: C F Abshire, J L Carroll & A-M Dragoi

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RNF168 cooperates with RNF8 to mediate FOXM1 ubiquitination and degradation in breast cancer epirubicin treatment

RNF168 cooperates with RNF8 to mediate FOXM1 ubiquitination and degradation in breast cancer epirubicin treatment

Oncogenesis 5, e252 (August 2016). doi:10.1038/oncsis.2016.57

Authors: M Kongsema, S Zona, U Karunarathna, E Cabrera, E P S Man, S Yao, A Shibakawa, U-S Khoo, R H Medema, R Freire & E W-F Lam

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KRAS mutation leads to decreased expression of regulator of calcineurin 2, resulting in tumor proliferation in colorectal cancer

KRAS mutation leads to decreased expression of regulator of calcineurin 2, resulting in tumor proliferation in colorectal cancer

Oncogenesis 5, e253 (August 2016). doi:10.1038/oncsis.2016.47

Authors: H Niitsu, T Hinoi, Y Kawaguchi, K Sentani, R Yuge, Y Kitadai, Y Sotomaru, T Adachi, Y Saito, M Miguchi, M Kochi, H Sada, M Shimomura, N Oue, W Yasui & H Ohdan

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Phase Ib study of duligotuzumab (MEHD7945A) plus cisplatin/5-fluorouracil or carboplatin/paclitaxel for first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck

BACKGROUND

This open-label, multicenter, phase Ib study assessed the safety and preliminary activity of duligotuzumab, a dual-action antibody that blocks ligand binding to human epidermal growth factor receptor 3 (HER3) and epidermal growth factor receptor, in combination with chemotherapy, in the first-line treatment of patients with recurrent/metastatic squamous cell cancer of the head and neck.

METHODS

On day 1, duligotuzumab at a dose of 1650 mg intravenously was combined with cisplatin at a dose of 100 mg/m² and 5-fluorouracil at a dose of 1000 mg/m²/day on days 1 to 4 in treatment arm A, or carboplatin (area under the curve, 6 mg/mL/min) and paclitaxel (at a dose of 200 mg/m²) in treatment arm B. Up to 6 cycles (21 days/cycle) were followed by duligotuzumab maintenance until disease progression or intolerable toxicity occurred.

RESULTS

Nine patients in arm A and 15 patients in arm B received a median of 6 cycles of chemotherapy, and a median of 11 cycles (arm A) and 9 cycles (arm B) of duligotuzumab. Dose-limiting toxicities occurred in 3 patients in arm A and 1 patient in arm B. Grade ≥ 3 treatment-related adverse events (graded according to graded according to National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]) in ≥ 3 patients were neutropenia (5 patients), hypokalemia (4 patients), dehydration (3 patients), anemia (3 patients), and diarrhea (3 patients) in arm A, and neutropenia (8 patients), anemia (5 patients), febrile neutropenia (4 patients), leukopenia (3 patients), thrombocytopenia (3 patients), and hypomagnesemia (3 patients) in arm B. The chemotherapy dose was reduced in 19 of 24 patients. Sixteen patients (67%) demonstrated objective responses regardless of human papillomavirus status or neuregulin 1 (NRG1) mRNA expression (arm A: 2 confirmed complete responses and 4 confirmed partial responses; arm B: 2 confirmed complete responses and 8 confirmed partial responses).

CONCLUSIONS

Duligotuzumab in combination with cisplatin/5-fluorouracil or carboplatin/paclitaxel demonstrated encouraging activity in patients with recurrent/metastatic squamous cell cancer of the head and neck; an association with increased frequency and severity of select adverse events relative to historical data was suggestive of the potentiation of chemotherapy-related adverse events. Cancer 2016. © 2016 American Cancer Society.

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Breast carcinoma with an Oncotype Dx recurrence score

BACKGROUND

A 21-gene expression assay (Oncotype DX recurrence score [RS]) that uses reverse transcriptase-polymerase chain reaction is used clinically in patients with early-stage, estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast carcinoma (ER+/HER2- BC) to determine both prognosis with tamoxifen therapy and the usefulness of adding adjuvant chemotherapy. Use of the assay is associated with reductions in overall chemotherapy use. The current study examined the treatments and outcomes in patients with low RS.

METHODS

The authors reviewed the institutional database to identify patients with lymph node-negative, ER+/HER2- BC who were treated at the study institution between September 2008 and August 2013 and their 21-gene RS results.

RESULTS

A total of 1406 consecutive patients with lymph node-negative ER+/HER2- BC and a low RS were identified (510 patients had an RS of 0-10 and 896 patients had an RS of 11-17). The median age at the time of diagnosis of BC was 56 years; 63 patients (4%) were aged <40 years. Overall, 1361 patients (97%) received endocrine therapy and 170 patients (12%) received chemotherapy. The median follow-up was 46 months. Six patients (0.4%) developed distant metastases (1 patient with an RS of 5 and 5 patients with an RS of 11-17). In the cohorts of patients with an RS of 11 to 17, the absolute rate of distant metastasis among patients aged <40 years was 7.1% (3 of 42 patients) versus 0.2% among patients aged ≥40 years (2 of 854 patients).

CONCLUSIONS

The data from the current study document a 0.4% rate of distant metastasis within 5 years of BC diagnosis among patients with lymph node-negative ER+/HER2- BC with an RS <18. Patients aged <40 years at the time of BC diagnosis were observed to have a higher rate of distant metastases. Analysis of data from other studies is necessary to validate this observation further. Cancer 2016. © 2016 American Cancer Society.

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Correlative analyses of RET and RAS mutations in a phase 3 trial of cabozantinib in patients with progressive, metastatic medullary thyroid cancer

BACKGROUND

Cabozantinib significantly prolonged progression-free survival (PFS) versus a placebo in patients with progressive, metastatic medullary thyroid cancer (MTC; P < .001). An exploratory analysis of phase 3 trial data evaluated the influence of rearranged during transfection (RET) and RAS (HRAS, KRAS, and NRAS) mutations on cabozantinib clinical activity.

METHODS

Patients (n = 330) were randomized to cabozantinib (140 mg/day) or a placebo. The primary endpoint was PFS. Additional outcome measures included PFS, objective response rates (ORRs), and adverse events in RET and RAS mutation subgroups.

RESULTS

Among all study patients, 51.2% were RET mutation–positive (38.2% with RET M918T), 34.8% were RET mutation–unknown, and 13.9% were RET mutation–negative. Sixteen patients were RAS mutation–positive. Cabozantinib appeared to prolong PFS versus the placebo in the RET mutation–positive subgroup (hazard ratio [HR], 0.23; 95% confidence interval [CI], 0.14-0.38; P < .0001), the RET mutation–unknown subgroup (HR, 0.30; 95% CI, 0.16-0.57; P = .0001), and the RAS mutation–positive subgroup (HR, 0.15; 95% CI, 0.02-1.10; P = .0317). The RET M918T subgroup achieved the greatest observed PFS benefit from cabozantinib versus the placebo (HR, 0.15; 95% CI, 0.08-0.28; P < .0001). The ORRs for RET mutation–positive, RET mutation–negative, and RAS mutation–positive patients were 32%, 22%, and 31%, respectively. No PFS benefit was observed in patients lacking both RET and RAS mutations, although the ORR was 21%. The safety profile for all subgroups was similar to that for the overall cabozantinib arm.

CONCLUSIONS

These data suggest that cabozantinib provides the greatest clinical benefit to patients with MTC who have RET M918T or RAS mutations. However, a prospective trial is needed to confirm the relation between genetic variation and the response to cabozantinib. Cancer 2016. © 2016 American Cancer Society.

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Activity of erlotinib when dosed below the maximum tolerated dose for EGFR-mutant lung cancer: Implications for targeted therapy development

BACKGROUND

Erlotinib is a standard first-line therapy for patients who have metastatic nonsmall cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The recommended dose of 150 mg daily is the maximum tolerated dose (MTD). Few clinical data are available regarding its efficacy at doses less than the MTD.

METHODS

An institutional database was queried for patients with advanced NSCLC who were positive for EGFR L858R mutations or exon 19 deletions and had received treatment with erlotinib. The treatment course, including the erlotinib dose at initiation of treatment, at 4 months into therapy, and at disease progression, was retrospectively studied. Progression-free survival (PFS) was compared between patients who received the MTD (150 mg) and those who received reduced-dose erlotinib (≤100 mg).

RESULTS

In total, 198 eligible patients were identified. Thirty-one patients (16%) were initiated on reduced-dose erlotinib; they were older (P = .001) and had lower performance status (P = .01) compared with those who were initiated on erlotinib at the MTD. The response rate to reduced-dose erlotinib was 77%. The median PFS of patients initiated on reduced-dose erlotinib was 9.6 months versus 11.4 months for those initiated at the MTD, a difference that was not statistically significant (hazard ratio, 0.81; 95% confidence interval, 0.54-1.21; P = .30). There was a nonsignificant trend toward higher rates of progression within the central nervous system with reduced-dose erlotinib.

CONCLUSIONS

At doses below the MTD, erlotinib treatment results in a high response rate and a prolonged median PFS. Review of the literature indicates that 15 of 30 small-molecule inhibitors that are approved or in late-stage development for cancer therapy have recommended doses below the MTD. When the toxicities of MTD dosing are a concern, an investigation of small-molecule inhibitors at doses below the MTD is warranted. Cancer 2016. © 2016 American Cancer Society.

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Precision, accuracy, and resolution—Dose selection of oral anticancer agents

To refine and individualize regimens, the dosing of oral anticancer agents in populations and in patients has to evolve. The additional use of tools to help refine doses should be used early in drug development. See also pages 000-000.

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Associations Between Decisional Balance and Health Behaviors Among Adult Cancer Survivors

Abstract

Interventions directed at health behavior change are increasingly being developed for cancer survivors. This study validates decisional balance measures for physical activity and fruit and vegetable (F/V) consumption among adult survivorship population. Participants were N = 86 patients who previously completed primary treatment for breast or prostate cancer for at least 5 years and were enrolled in an e-health intervention that aimed to improve physical activity and nutrition behaviors. Decisional balance, stage of change, F/V consumption, and physical activity were assessed at baseline and 3 months. Factor analysis was used to assess the structure of the decisional balance measures. The relationship between decisional balance, stage, and behavioral outcomes was assessed with mixed model analyses. The two factor structures of each measure were supported. Pros and cons differed across stages of change for both behaviors (p's < .0001). Total Metabolic Equivalent of Task units (METs) were related to decisional balance pros (p = .012) and cons (p = .003). F/V consumption was significantly associated with decisional balance pros (p = .0003), but not cons (p = .112). Overall, findings provide validation for these decisional balance measures as indicators of health behaviors and support the value of using these measures in further research to aid in understanding of behavior change in this population.

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