Phase II trial of hypofractionated VMAT-based treatment for early stage breast cancer: 2-year toxicity and clinical results

Abstract

Background

To report toxicity and early clinical outcomes of hypofractionated simultaneous integrated boost (SIB) approach with Volumetric Modulated Arc Therapy (VMAT) as adjuvant treatment after breast-conserving surgery.

Methods

Patients presenting early-stage breast cancer were enrolled in a phase II trial. Eligibility criteria: age > 18 years old, invasive cancer or ductal carcinoma in situ (DCIS), Stage I-II (T < 3 cm and N ≤ 3), breast-conserving surgery without oncoplastic reconstruction. Any systemic therapy was allowed in neoadjuvant or adjuvant setting. All patients underwent VMAT-SIB technique to irradiate the whole breast and the tumor bed. Doses to whole breast and surgical bed were 40.5 Gy and 48 Gy, respectively, delivered in 15 fractions over 3 weeks. Acute and late skin toxicities were recorded. Cosmetic outcome was assessed as excellent/good or fair/poor.

Results

The present study focused on results of a cohort of 144 patients with a minimum follow-up of 24 months (median 37, range 24–55 months). Median age was 62 years old (range 30–88). All patients had an invasive carcinoma (no patients with DCIS were present in this subset). At one year, the highest reported skin toxicity was G1, in 14 % of the patients; this data dropped to 4 % at the last follow-up, after more than 2 years. Breast pain was recorded in 21.6 % of the patients 6 months after treatment, while it was present in 3.5 % of the patients at the last follow-up, showing a significant improvement with time. Correlation between liponecrosis and boost target volume was found not significant. Breast pain was correlated with breast volume. No pulmonary or cardiological toxicities were recorded. After an early evaluation of clinical outcomes, only one case presented disease relapse, as liver metastases.

Conclusions

The 3-week VMAT-SIB course as adjuvant treatment after breast-conserving surgery showed to be well tolerated and was associated with optimal local control. Long-term follow-up data are needed to assess late toxicity and clinical outcomes.

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Connectivity map identifies HDAC inhibition as a treatment option of high-risk hepatoblastoma.

Connectivity map identifies HDAC inhibition as a treatment option of high-risk hepatoblastoma.

Cancer Biol Ther. 2016 Sep 16;:0

Authors: Beck A, Eberherr C, Hagemann M, Cairo S, Häberle B, Vokuhl C, von Schweinitz D, Kappler R

Abstract
Hepatoblastoma (HB) is the most common liver tumor of childhood, usually occurring in children under the age of three years. The prognosis of patients presenting with distant metastasis, vascular invasion and advanced tumor stages remains poor and children that do survive often face severe late effects from the aggressive chemotherapy regimen. To identify potential new therapeutics for high risk HB we used a 1,000-gene expression signature as input for a Connectivity Map (CMap) analysis, which predicted histone deacetylase (HDAC) inhibitors as a promising therapy option. Subsequent expression analysis of primary HB and HB cell lines revealed a general overexpression of HDAC1 and HDAC2, which has been suggested to be predictive for the efficacy of HDAC inhibition. Accordingly, treatment of HB cells with the HDAC inhibitors SAHA and MC1568 resulted in a potent reduction of cell viability, induction of apoptosis, reactivation of epigenetically suppressed tumor suppressor genes, and the reversion of the 16-gene HB classifier towards the more favorable expression signature. Most importantly, the combination of HDAC inhibitors and cisplatin - a major chemotherapeutic agent of HB treatment - revealed a strong synergistic effect, even at significantly reduced doses of cisplatin. Our findings suggest that HDAC inhibitors skew HB cells towards a more favorable prognostic phenotype through changes in gene expression, thus indicating a targeted molecular mechanism that seems to enhance the anti-proliferative effects of conventional chemotherapy. Thus, adding HDAC inhibitors to the treatment regimen of high risk HB could potentially improve outcomes and reduce severe late effects.

PMID: 27635950 [PubMed - as supplied by publisher]

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Expression of steroid hormone receptors and its prognostic significance in urothelial carcinoma of the upper urinary tract.

Expression of steroid hormone receptors and its prognostic significance in urothelial carcinoma of the upper urinary tract.

Cancer Biol Ther. 2016 Sep 16;:0

Authors: Kashiwagi E, Fujita K, Yamaguchi S, Fushimi H, Ide H, Inoue S, Mizushima T, Reis LO, Sharma R, Netto GJ, Nonomura N, Miyamoto H

Abstract
To assess the expression status of steroid hormone receptors in upper urinary tract urothelial carcinoma (UUTUC), we immunohistochemically stained for androgen receptor (AR), estrogen receptor-α (ERα), ERβ, glucocorticoid receptor (GR), and progesterone receptor (PR) in 99 UUTUC specimens and paired non-neoplastic urothelial tissues. AR/ERα/ERβ/GR/PR was positive in 20%/18%/62%/63%/16% of tumors, which was significantly lower (except PR) than in benign urothelial tissues [57% (P<0.001)/40% (P = 0.001)/85% (P = 0.001)/84% (P = 0.002)/13% (P = 0.529)]. There were no significant associations between each receptor expression pattern and histopathological characteristic of the tumors including tumor grade/stage. Kaplan-Meier and log-rank tests revealed no significant prognostic value of each receptor expression in these 99 patients. However, patients with UUTUC positive for either ERα or PR had a significantly higher risk of disease-specific mortality (P = 0.025), compared with those with UUTUC negative for both. PR positivity alone in pT3 or pT4 tumors was also strongly associated with the risk of disease-specific mortality (P = 0.040). Multivariate analysis further identified the expression of ERα and/or PR as a strong predictor for disease-specific mortality in the entire cohort of the patients (hazard ratio, 2.434; P = 0.037). Thus, in accordance with previous observations in bladder specimens, significant decreases in the expression of AR/ERα/ERβ/GR in UUTUC, compared with that in non-neoplastic urothelium, were observed. Meanwhile, the negativity of both ERα and PR in UUTUC as well as the negativity of PR alone in deeply invasive tumor was suggested to serve as a prognosticator.

PMID: 27635763 [PubMed - as supplied by publisher]

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Clinicopathological Characteristics and Survival of ALK, ROS1 and RET rearrangements in Non-Adenocarcinoma Non-Small Cell Lung Cancer Patients.

Clinicopathological Characteristics and Survival of ALK, ROS1 and RET rearrangements in Non-Adenocarcinoma Non-Small Cell Lung Cancer Patients.

Cancer Biol Ther. 2016 Sep 16;:0

Authors: Song Z, Yu X, Zhang Y

Abstract
BACKGROUND: ALK, ROS1 and RET rearrangements represent three most frequent fusion genes in non-small cell lung cancer (NSCLC). Rearrangements of these three genes exist predominantly in lung adenocarcinoma while rarely in non-adenocarcinoma. Our objective was to explore the frequency, clinicopathological characteristics and survival of ALK, ROS1 and RET rearrangements in non-adenocarcinoma NSCLC patients.
METHODS: ALK, ROS1 and RET rearrangements were screened by reverse transcriptase polymerase chain reaction (RT-PCR) in patients with completely resected non-adenocarcinoma NSCLC. All positive samples were confirmed with fluorescence in situ hybridization (FISH). Survival analysis was performed with Kaplan-Meier method and log-rank for comparison.
RESULTS: A total of 385 patients underwent complete resection, including squamous cell carcinoma (n = 245), adenosquamous carcinoma (n = 85) and large cell carcinoma (n = 55). Twelve of them were identified as harboring fusion genes, including ALK (n = 7), ROS1 (n = 3) and RET (n = 2) rearrangements. The fusion frequencies of adenosquamous, squamous cell and large cell carcinomas were 8.2%, 1.6% and 1.8% respectively. Their median age was 49.5 years and 3 of them had a smoking history. No survival difference existed between fusion gene positive and negative patients (36.7 vs.50.2 months, P = 0.21).
CONCLUSION: The frequencies of ALK, ROS1 and RET rearrangements are low in non-adenocarcinoma NSCLC patients. And their clinical characteristics are similar to those in lung adenocarcinoma. Fusions of the above three genes are not prognostic factor for non-adnocarcinoma NSCLC patients.

PMID: 27635639 [PubMed - as supplied by publisher]

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Clinician and Parent Perspectives on Educational Needs for Increasing Adolescent HPV Vaccination

Abstract

Human papillomavirus (HPV)-related morbidity and mortality remain a significant public health burden despite the availability of HPV vaccines for cancer prevention. We engaged clinicians and parents to identify barriers and opportunities related to adolescent HPV vaccination within a focused geographic region. This mixed-method study design used an interviewer-administered semi-structured interview with clinicians (n = 52) and a written self-administered survey with similar items completed by parents (n = 54). Items focused on experiences, opinions, and ideas about HPV vaccine utilization in the clinical setting, family, and patient perceptions about HPV vaccination and potential future efforts to increase vaccine utilization. Quantitative items were analyzed using descriptive statistics, while qualitative content was analyzed thematically. Suggested solutions for achieving higher rates of HPV vaccination noted by clinicians included public health education, the removal of stigma associated with vaccines, media endorsements, and targeting parents as the primary focus of educational messages. Parents expressed the need for more information about HPV-related disease, HPV vaccines, vaccine safety, sexual concerns, and countering misinformation on social media. Results from this mixed-method study affirm that educational campaigns targeting both health care professionals and parents represent a key facilitator for promoting HPV vaccination; disease burden and cancer prevention emerged as key themes for this messaging.

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Sulforaphane Regulates NFE2L2/Nrf2-Dependent Xenobiotic Metabolism Phase II and Phase III Enzymes Differently in Human Colorectal Cancer and Untransformed Epithelial Colon Cells.

Sulforaphane Regulates NFE2L2/Nrf2-Dependent Xenobiotic Metabolism Phase II and Phase III Enzymes Differently in Human Colorectal Cancer and Untransformed Epithelial Colon Cells.

Nutr Cancer. 2016 Sep 16;:1-11

Authors: Lubelska K, Wiktorska K, Mielczarek L, Milczarek M, Zbroińska-Bregisz I, Chilmonczyk Z

Abstract
Sulforaphane (SFN), a naturally occurring chemopreventive and anticancer agent, is a nuclear factor, erythroid 2-like 2 (NFE2L2/Nrf2) inducer. Nrf2 plays a critical role in coordinating the cell defense system by initiating the transcription of cytoprotective genes, including detoxification enzymes such as NAD(P)H quinone dehydrogenase 1 (NQO1) and transport proteins such as ATP-binding cassette, subfamily C (CFTR/MRP). Recently, the essential role of Nrf2 in tumor development and progression and in the development of multidrug resistance in cancer cells has been highlighted. The aim of this study was to compare the effect of SFN on the Nrf2 system and the Nrf2-target enzymes NQO1 and MRP in human untransformed epithelial colon CRL-1790 cells and in HT-29 and Caco-2 colorectal cancer cells to elucidate the role of SFN in cancer prevention and treatment. We have demonstrated that SFN has excellent cytoprotective properties in CRL-1790 cells, as it induced Nrf2-dependent expression of MRP1 and NQO1. SFN induced Nrf2 target enzyme activity in HT-29 and Caco-2 cancer cells but regulated the Nrf2/ARE signaling pathway differently in cancer and untransformed cells.

PMID: 27636860 [PubMed - as supplied by publisher]

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Association between Dietary Inflammatory Index and Gastric Cancer Risk in an Italian Case-Control Study.

Association between Dietary Inflammatory Index and Gastric Cancer Risk in an Italian Case-Control Study.

Nutr Cancer. 2016 Sep 16;:1-7

Authors: Shivappa N, Hébert JR, Ferraroni M, La Vecchia C, Rossi M

Abstract
BACKGROUND: In this study, we explored the association between the dietary inflammatory index (DII) and gastric cancer risk in an Italian case-control study.
MATERIALS AND METHODS: Cases were 230 patients with incident, histologically confirmed cases of gastric cancer from the Greater Milan area, Northern Italy. Controls were 547 frequency-matched subjects admitted to the same network of hospitals as cases for a wide spectrum of acute, non-neoplastic conditions. The DII was computed using a reproducible and valid 78-item food frequency questionnaire. Odds ratios (ORs) were estimated through logistic regression models conditioned on age and sex and adjusted for recognized confounding factors, including total energy intake.
RESULTS: Subjects with the most pro-inflammatory diet had a higher risk of gastric cancer compared to subjects with the most anti-inflammatory diet (ORQuartile4vs1 = 2.35, 95% confidence interval, 1.32, 4.20; P-trend = 0.004).
CONCLUSION: These results indicate that a pro-inflammatory diet, as indicated by higher DII score, was associated with increased risk of gastric cancer.

PMID: 27636679 [PubMed - as supplied by publisher]

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