Factors associated with long-term altered well-being after prophylactic bilateral salpingo-oophorectomy, namely, lower quality of life, altered sexual functioning, greater anxiety, and more endocrine symptoms, were identified.

Learning Objectives

After completing this course, the reader will be able to: Describe factors associated with decreased well-being after PBSO in order to prospectively identify patients at risk.Provide pre-operative counseling and information to patients at risk of decreased well-being after PBSO.

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Background.

Prophylactic bilateral salpingo-oophorectomy (PBSO) might alter several components of well-being, such as sexual functioning and endocrine symptoms, in women at high risk for hereditary breast and/or ovarian cancer, compared with the general population. We searched for factors associated with altered long-term well-being in this population (lower quality of life [QOL], altered sexual functioning, greater anxiety, more endocrine symptoms).

Methods.

All high-risk women who had undergone PBSO during the past 15 years in a single cancer center were contacted by mail. Upon acceptance, they were sent five questionnaires: (a) general social questions, (b) the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30, (c) Sexual Activity Questionnaire, (d) Functional Assessment of Cancer Therapy – Endocrine Symptom, and (5) State-Trait Anxiety Inventory. Logistic analyses were used to identify factors associated with altered results. Because of multiple testing, only p-values ≤ .01 were considered significant.

Results.

One hundred twelve of 175 women (64%) returned the completed questionnaires at a mean duration (standard deviation) of 6.0 (5.1) years after PBSO. QOL was positively influenced by two baseline factors: a high educational level and occupying an executive position. However, younger age at PBSO was associated with lower social functioning and greater anxiety. At the time of the study, practicing a sport and the avoidance of weight gain (≥10%) were highly related to QOL, sexual pleasure, endocrine symptoms, and anxiety in the univariate analysis and predictive of better QOL and lower anxiety in the multivariate analysis.

Conclusions.

Younger women and women with a low educational level and no occupation appear to be at higher risk for altered long-term well-being. After surgery, practicing a sport and stable weight may help maintain overall well-being.

Objective

Recent recommendations regarding indications of accelerated partial breast irradiation (APBI) have been put forward for selected breast cancer (BC) patients. However, some treatment planning parameters, such as total dose, are not yet well defined. The Institut Gustave Roussy has initiated a dose escalation trial at the 40 Gy/10 fractions/5 days and at a further step of total dose (TD) of 42 Gy/10 fractions/ 5 days. Here, we report early results of the latest step compared with the 40 Gy dose level.

Methods and materials

From October 2007 to March 2010, a total of 48 pT1N0 BC patients were enrolled within this clinical trial: 17 patients at a TD of 42 Gy/10f/5d and 31 at a TD of 40 Gy/10f/5d. Median follow-up was 19 months (min-max, 12–26). All the patients were treated by APBI using a technique with 2 minitangents and an “enface” electrons delivering 20% of the total dose. Toxicities were systematically assessed at 1; 2; 6 months and then every 6 months.

Results

Patients’ recruitment of 42 Gy step was ended owing to persistent grade 3 toxicity 6 months after APBI completion (n = 1). Early toxicities were statistically higher after a total dose of 42 Gy regarding grade ≥2 dry (p = 0.01) and moist (p = 0.05) skin desquamation. Breast pain was also statistically higher in the 42 Gy step compared to 40 Gy step (p = 0.02). Other late toxicities (grade ≥2 fibrosis and telangectasia) were not statistically different between 42 Gy and 40 Gy.

Conclusions

Early toxicities were more severe and higher rates of late toxicities were observed after 42 Gy/10 fractions/5 days when compared to 40 Gy/10 fractions/5 days. This data suggest that 40 Gy/10 fractions/ 5 days could potentially be the maximum tolerance for PBI although longer follow-up is warranted to better assess late toxicities.

The success of anticancer chemotherapy relies at least in part on the induction of an immune response against tumor cells. Thus, tumors growing on mice that lack the pattern recognition receptor TLR4 or the purinergic receptor P2RX7 fail to respond to chemotherapy with anthracyclins or oxaliplatin in conditions in which the same neoplasms growing on immunocompetent mice would do so. Similarly, the therapeutic efficacy (measured as progression-free survival) of adjuvant chemotherapy with anthracyclins is reduced in breast cancer patients bearing loss-of-function alleles of TLR4 or P2RX7. TLR4 loss-of-function alleles also have a negative impact on the therapeutic outcome of oxaliplatin in colorectal cancer patients. Here, we report that loss-of-function TLR4 and P2RX7 alleles do not affect overall survival in non-small cell lung cancer (NSCLC) patients, irrespective of the administration and type of chemotherapy. The intrinsic characteristics of NSCLC (which near-to-always is chemoresistant and associated with poor prognosis) and/or the type of therapy that is employed to treat this malignancy (which near-to-always is based on cisplatin) may explain why two genes that affect the immune response to dying cells fail to influence the clinical progression of NSCLC patients.

This study determined whether expression levels of a panel of biologically relevant microRNAs can be used as prognostic or predictive biomarkers in patients who participated in the International Adjuvant Lung Cancer Trial (IALT), the largest randomized study conducted to date of adjuvant chemotherapy in patients with radically resected non-small cell lung carcinoma (NSCLC). Expression of miR-21, miR-29b, miR-34a/b/c, miR-155 and let-7a was determined by quantitative real-time PCR in paraffin embedded formalin fixed tumor specimens from 639 IALT patients. Prognostic and predictive value of microRNA expression for survival were studied using a Cox model, which included every factor used in the stratified randomization, clinicopathological prognostic factors and other factors statistically related to microRNA expression. Investigation of the expression pattern of microRNAs in situ was performed. We also analyzed association of TP53 mutation status and miR-34a/b/c expression, EGFR and KRAS mutation status and miR-21 and Let-7a expression, respectively. Finally, association of p16 and miR-29b expression was assessed. Overall, no significant association was found between any of the tested microRNAs and survival, with the exception of miR-21 where a deleterious prognostic effect of lowered expression was suggested. Otherwise, no single or combinatorial microRNA expression profile predicted response to adjuvant cisplatin-based chemotherapy. Together, our results indicate that the miRNA expression patterns examined were neither predictive nor prognostic in a large patient cohort of radically resected NSCLC randomized to receive adjuvant cisplatin-based chemotherapy versus follow-up only.

Background

Accurate localisation of the lumpectomy cavity (LC) volume is one of the most critical points in 3D-conformal Partial breast irradiation (3D-APBI) treatment planning because the irradiated volume is restricted to a small breast volume. Here, we studied the role of the placement of surgical clips at the 4 cardinal points of the lumpectomy cavity in target delineation.

Methods

Forty CT-based 3D-APBI plans were retrieved on which a total of 4 radiation oncologists, two trainee and two experienced physicians, outlined the lumpectomy cavity. The inter-observer variability of LC contouring was assessed when the CTV was defined as the delineation that encompassed both surgical clips and remodelled breast tissue.

Results

The conformity index of tumour bed delineation was significantly improved by the placement of surgical clips within the LC (median at 0.65). Furthermore, a better conformity index of LC was observed according to the experience of the physicians (median CI = 0.55 for trainee physicians vs 0.65 for experienced physicians).

Conclusions

The placement of surgical clips improved the accuracy of lumpectomy cavity delineation in 3D-APBI. However, a learning curve is needed to improve the conformity index of the lumpectomy cavity.