Les micrométastases : entité biologique et réalité clinique ?

Micrometastases or sub-micrometastases can be detected by standard histopathological method sometimes associated with immunohistochemistry in lymph nodes, bone marrow and blood. The consequence of these small size involvement may be prognostic and therapeutic. Two factors are necessary to assess this kind of involvement: the rate of involvement of non-sentinel lymph node after axillary lymph node dissection and significative difference of survivals. The rate of involvement of non-sentinel lymph node in case of micrometastases or sub-micrometastases is different from the rate of involvement in case of no lymph node metastases (7 to 8%) or in case of macrometases (30 to 50%). Micrometastase is an important factor to determine the rate of involvement of non-sentinel lymph node, the overall or disease free survival and to assess the need of radiotherapy and chemotherapy. In conclusion, micrometastases and sub-micrometastases have a clinical impact even if complementary axillary lymph node dissection is still discussed.     

Strategies for screening for pancreatic adenocarcinoma in high-risk patients

Screening high-risk individuals with imaging tests, such as endoscopic ultrasound and computed tomography, can lead to the detection and treatment of predominantly asymptomatic premalignant lesions. These pancreatic lesions consist of resectable, mostly branch-type non-invasive intraductal papillary mucinous neoplasms. Endoscopic ultrasound features of chronic pancreatitis are highly prevalent in high-risk individuals and these directly correlate with multifocal lobulocentric parenchymal atrophy due to pancreatic intraepithelial neoplasia. Long-term, multi-prospective studies are needed to determine if screening for early pancreatic adenocarcinoma and timely intervention will result in decreased pancreatic cancer incidence and mortality in high-risk individuals.     

Qualité de vie dans les cancers gynécologiques : actualités

The evaluation of quality of life has become essential in gynecological oncology. Recent guidelines have been published to improve the collection, analysis and publication of the data quality of life that will make them more reliable, reproducible and integrate them into the final treatment decision. This year at ASCO, in breast cancer, the benefit of sentinel lymph node dissection compared to the quality of life has been demonstrated. New data on cognitive function in patients treated for breast cancer show the importance of the evaluation of these disorders especially among elderly patients who are at-risk populations. Medical strategies including targeted therapies can improve survival without impairing the quality of life, also with improved gastrointestinal symptoms in case of combination chemotherapy with bevacizumab in patients with ovarian cancer in a situation early recurrence. Similarly, the addition of a pathway inhibitor M- Tor (everolimus) with hormonal therapy does not induce degradation of the quality of life in women with metastatic breast cancer.     

Assessment of daily physical activity of breast cancer patients and comparison with two control populations

ObjectiveThe purpose is to assess the physical activity of breast cancer patients using a questionnaire, the Population Physical Activity Questionnaire (POPAQ) and to compare the data with those from two female populations: one healthy population and one with a previous history of cardiovascular disease.Patients and methodsThis prospective study included 104 consecutive breast cancer patients who were addressed at the radiation oncology department, Institut de cancérologie de la Loire from March to July 2010. A questionnaire using factorial method was used for assessment of physical activity.ResultsIn the study population, the rest energetic expenditures of physical energy related to both rest activity and low intensity activity were higher than in the healthy patients (5 292 ± 1 376 versus 5 520 ± 1 248 kJ/24 h, P < 0.05 and 2 583 ± 681 versus 2 494 ± 558 kJ/24 h, P < 0.05, respectively). Conversely, the energetic expenditures of physical energy related to both high physical activity and intensive physical activity were lower than in the healthy population (882 ± 441 versus 1 560 ± 868 kJ/24 h, P < 0.05 et 210 ± 274 versus 340 ± 621 kJ/24 h, P < 0.05, respectively).ConclusionThe POPAQ allows quantifying the daily physical activity and seems feasible in clinical routine in breast cancer patients. In our study, it was found that the physical activity of those patients was significantly different from that of a healthy population. Further investigations are necessary for better defining the true impact of such differences in terms of incidence and prognostic for mammary carcinoma.     

Prévention et dépistage des cancers

We show that cancer mortality is decreasing with time for most sites of cancer, the most notable exception being lung cancer in women. Cancer incidence is a misleading indicator because it can depend on diagnostic procedures, as observed with prostate cancer in men and breast or thyroid cancer in women. Overall these data contradict the alarming information that cancer is on the increase, which is widespread by the media and some health professionals. To be efficient in the prevention of cancer one needs to identify its causes and measure their relative importance. The major causes of cancer in France today are tobacco and alcohol. The variations of the price of tobacco and their effects on sales show the importance of the taxation policy.Cancer screening is practised in a way defying logic : a screening procedure with a demonstrated high efficacy is not part of a national programme whereas a useless and even potentially harmful procedure is very widely used.     

Clinical practice of breast cancer protontherapy: A single-centre experience from selection to treatment

PurposeBreast protontherapy efficiently limits cardiac, lung and contralateral breast exposure, which may clinically translate into better late tolerance profile compared with classic photon techniques. While breast protontherapy is already implemented in the United States and in some European countries, clinical experience of breast cancer protontherapy is currently limited in France. The aim of this study is to evaluate the clinical practice of breast cancer protontherapy at the Institut Curie in order to implement this technique at a larger scale.Materials and methodsData from all breast cancer patients that have been addressed to the protontherapy centre of Orsay (CPO, Institut Curie) for adjuvant breast protontherapy were retrieved. We analysed why these patients were ultimately treated with protontherapy or not.ResultsBetween November 2019 and November 2020, eleven breast cancer patients have been evaluated for adjuvant protontherapy at the CPO. Two of them were ultimately treated with proton beams; adjuvant breast protontherapy therapy was well tolerated. The nine other patients were not treated with protontherapy due to lack of availability of protontherapy treatment rooms in acceptable time limits, at the time of patient evaluation.ConclusionDespite dosimetric advantages and excellent clinical tolerance, lack of availability of protontherapy machines currently limits wider implementation of breast protontherapy.     

Chemotherapy of metastatic pancreatic adenocarcinoma: challenges and encouraging results

The outcome for patients with metastatic pancreatic ductal adenocarcinoma is dismal. In this article, we will review current first-line treatments for metastatic pancreatic adenocarcinoma focusing on phase III randomized studies. Single-agent gemcitabine, the reference treatment since 1995, offers only slight benefit. Numerous trials using gemcitabine in combination with different cytotoxic agents have resulted in no major improvement compared to gemcitabine alone. Only the gemcitabine-erlotinib combination has shown a small, but statistically improvement in survival. In selected patients with good performance status ECOG 0-1, no cardiac ischemia and almost normal bilirubin level, the Folfirinox regimen, when compared to gemcitabine as single agent, was associated with more toxicities, but also with significant increased survival and delay in the degradation of quality of life. So, Folfirinox is a new more toxic and more efficient regimen that may be considered in patients with good performance status.     

Research on body image in oncology: a methodological synthesis

Cancer and its treatments induce important physical transformations, which could be source of psychological and social difficulties. Since about 15 years, interest for cancer and treatments consequences on body image had grown in oncology. Nevertheless studying body image remains complex because of conceptual and methodological limits. This article aims at a clarification about the methods employed in the field of cancer to assess body image, in order to make accessible reference marks about adapted instruments for every person who would like to study this theme.     

Perception accuracy of BRCA1/2 mutation predisposition in breast cancer women and associated factors

This study aims to determine accuracy between perceived risk of genetic predisposition and objective estimation of this risk, and its associated factors in women, probands affected with breast cancer. Perception of this risk, absolute and comparative, was confronted with objective estimation. Emotional distress and knowledge postcounseling were measured, respectively by the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES) and the Breast Genetic Counseling Knowledge Questionnaire (BGKQ). On 213 eligible consultants, the 173 questionnaires (81.2%) analyzed revealed an inaccuracy of perception of absolute and comparative risks in 50 and 55.3%, respectively. An unsignificant tendency to overestimate the absolute risk (p=0,08) and a significant underestimation of comparative risk (p<0.001) appear. The inaccuracy of the perception of absolute risk is associated with greater distress (β=0.150) and a lower educational level (β=-0.164), while the comparative risk is associated with higher knowledge (β=0.208), higher level of education (β=0.176) and a younger age (β=-0.151). Living in couple is a factor of inaccuracy of both form of risk assessment (β=0.189, β=0.147). While the adequacy of the perceived risk of carrying a mutation in a BRCA1 /2 should promote an informed decision about genetic testing and anticipation of its outcome, a large number of consultants does not apprehend this risk correctly when they have emotional distress and despite knowledge of the risk of breast cancer.     

Radiothérapie partielle du sein

Owing to breast cancer screening, breast cancer is more and more diagnosed at early stage. For those breast cancer women, breast conserving treatment (breast conserving surgery followed by whole breast irradiation) is commonly used since many years. New radiation modalities have been recently developed in early breast cancers particularly accelerated partial breast irradiation (APBI). Among all techniques of radiotherapy, 3D-conformal APBI and intraoperative radiotherapy (IORT) are the main modalities of radiotherapy used. The present review states on indications, treatment modalities and updated results of local control and side effects of partial breast irradiation.     

Follow-up in patients with early breast cancer

Breast cancer incidence remains the highest among gynaecologic neoplasms. Once they have achieved their treatments, patients should undergo careful follow-up. It aims at detecting early local recurrence or controlateral breast cancer. Based on large cohorts, clinical and radiological follow-up procedures come from guidelines realised by scientific organisations. We evaluated our regional practices in Franche-Comté and compared them to current guidelines. Patients with early breast cancer positive for hormonal receptors filled a questionnaire concerning their follow-up. It included patients treated from 1999 to 2005. When frequency of consultation is evaluated, only half of the patients undergo what is recommended. Whereas mammography and non-validated complementary exams are more regularly realised. Patients consulting more one practician have a better compliance. Our study underlines significant disparities among patients follow-up. Better interactions between physicians and a greater implication of patients in their follow-up would increase its quality.     

Antihormonal therapy in breast cancer and mTOR inhibitors

Hormonal dependence of breast cancer has been known for a long time, yet about half of breast cancers with estrogen receptor will not respond to antihormonal therapy. Now, we know that this resistance may be related to a dysfunction of the estrogen pathway, or that of growth factors and particularly the pathway of cell activation PI3K/Akt/mTOR. Prevention of these different mechanisms of resistance could involve combination therapies such as anti-estrogens (SERMs, aromatase inhibitors) with inhibitors of the activity of growth factors that are particularly temsirolimus and everolimus for the activation pathway cell PI3K/Akt/mTOR.     

Psychological and physical impact in women treated for breast cancer: Need for multidisciplinary surveillance and care provision

PurposeCancer survivors often experience adverse physical and psychosocial effects. Fear of recurrence is a difficulty very commonly reported in post-cancer life. The primary objective of this study was to describe post-cancer supportive care needs in patients treated for breast cancer.Patients and methodsIn this monocentric observational study, cancer survivors aged ≥ 18 years, diagnosed with breast cancer and treated in 2017 (cohort A) and in 2015 (cohort B) were administered a post-cancer needs questionnaire, and the Fear of Cancer Recurrence Inventory (severity subscale).ResultsThe study included 139 patients. Pain (51.9%), fatigue (51.9%), weight gain during treatment (35.1%), psychological difficulties (20.5%), and difficulties in marriage and sexual life (13.1%) were the complaints in the post-cancer period. There were no differences between the two cohorts. The severity subscale of the Fear of Cancer Recurrence Inventory showed 35.8% patients with a score > 13. The fear of recurrence was a source of social difficulties, psychological disorders, and difficulties in marriage and sexual life.ConclusionsNot only FCR, but also issues such as fatigue, pain, psychological difficulties, and difficulties in marriage and sexual life all call for a psycho-oncological follow-up. Clinical and radio-senological surveillance is essential, but it absolutely must be accompanied by a multidisciplinary follow-up, with central importance to psychological care.     

Métastases cérébrales de cancer du sein : facteurs pronostiques et prise en charge intégrée

During the last decades, advances in diagnostic and therapeutic technologies have modified the management of brain metastases, which is currently tailored to the type of primary site and to prognostic factors isolated in multivariate analyses. The aim of this article is to take stock of the current state of knowledge regarding prognostic factors in the setting of brain metastases from breast cancer as well as prognostic classifications proposed in this context. An appropriate multidisciplinary treatment for each prognostic class will be then discussed in light of the results of major randomized controlled trials enrolling patients with brain metastases from breast cancer.     

Brain metastases from breast cancer: usefulness and limits of prognostic scores

Approximately 10 to 30% of patients with metastatic breast cancer will develop brain metastases (BM) during the disease course. Whole-brain radiation therapy (WBRT) is considered the standard treatment for most patients, particularly those with extensive intracranial disease, providing symptom relief and increasing median and overall survival. Despite WBRT, the prognosis for the general population of patients with BM remains poor, with a median survival time of approximately five months. Several studies have examined the relative contributions of patient characteristics to survival and have attempted to identify subgroups of patients with substantially different outcomes in order to tailor therapy and to influence the design, stratification and interpretation of future clinical trials. This review examines prognostic scores and their validation in patients with BM from breast carcinoma. We also discuss the prognostic value of specific parameters for breast carcinoma, such as tumor HR status, HER2 over-expression or specific treatment parameters, and the value and limits of these prognostic scores in clinical practice.     

(18F)-FDG PET/CT parameters to predict survival and recurrence in patients with locally advanced cervical cancer treated with chemoradiotherapy

Purpose

To identify predictive (¹⁸F)-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT)-based parameters for locoregional control, disease-free survival and overall survival, by testing different thresholds of metabolic tumor volume and total lesion glycolysis in patients with locally-advanced cervical cancer.

A new scoring system for the diagnosis of BRCA1/2 associated breast-ovarian cancer predisposition

Criteria have been proposed for genetic testing of breast and ovarian cancer susceptibility genes BRCA1 and BRCA2. Using simulations, this study evaluates the efficiency (sensitivity, positive predictive value [PPV] and specificity) of the various criteria used in France. The efficiency of the criteria published in 1998, which are largely used, is not optimal. We show that some extensions of these criteria provide an increase in sensitivity with a low decrease in specificity and PPV. The study shows that scoring systems (Manchester, Eisinger) have similar efficiency that may be improved. In this aim, we propose a new scoring system that takes into account unaffected individuals and kinship coefficients between family members. This system increases sensitivity without affecting PPV and specificity. Finally, we propose a two-step procedure with a large screening by the physician for recommending genetic counselling, followed by a more stringent selection by the geneticist for prescribing genetic testing. This procedure would result in an increase of genetic counselling activity but would allow the identification of almost 80% of mutation carriers among affected individuals, with a mutation detection rate of 15% and a specificity of 88%.     

Réentraînement à l’activité physique dans la prise en charge globale du cancer du sein : étude pilote monocentrique

ObjectivesThe objective of the present study is to report the pilot experience at the « Loire cardiorespiratory readaptation center » of re-entrainment of physical activity for patients suffering from breast cancer.Patients and methodsBetween January 2012 and February 2013, 63 patients took the program at the readaptation center. The program is composed of three sessions a week during seven weeks. During the care, a medical team intervenes. It is composed of a cardiologist, a physiotherapist, a sophrologist, a psychologist and a dietician who take part in turns and/or together.ResultsDuring the first session of the program, the warm-up power chosen on the exercise bike was on average of 14.72 watts (min = 5; max = 30), and it went up to 44.84 watts (min = 15; max = 85) on average during the last session. The maximal power used by the patient was on average of 39.08 watts (min = 10; max = 70) during the first session. On the last day of training, the average maximal power between the patients was of 76.03 watts (min = 30; max = 110).ConclusionThe tests used into practice tend to confirm a physical progression between the beginning and the end of the re-training program. This study particularly shows that it is possible today to propose this type of program to the patients in daily practice.     

Evaluation of a software for automatic delineation of the mammary gland and organs at risk in patients treated for breast cancer in lateral position

Purpose of the studyThe purpose of this study was to assess the potential for improvement of routine breast and organs at risk contouring in patients treated in the lateral decubitus position using Workflow Box™ (Mirada Medical™, UK) automatic contouring software.Materials and methodsAutomatic contouring of the breast by this software is currently based on an atlas created from isodoses representing 95% of the prescribed dose in a population of patients previously treated at institut Curie. Forty cases of breast cancer (20 right breasts and 20 left breasts) were contoured by three radiation oncologists specialized in breast cancer, allowing the creation of a new atlas in the automatic contouring software. This study assessed the quality of contouring in 20 patients (ten right breasts and ten left breasts) by comparing manual contouring performed by the expert radiation oncologists (reference) with those generated by the old and new atlases developed at Institut Curie. The accuracy of contouring was assessed by overlap volume and the associated standard deviations.ResultsBreast contouring based on the new atlas and by radiation oncologists presented a mean overlap of 0.80 ± 0.09 for the right breast and 0.81 ± 0.06 for the left breast. By comparing volumes of interest contoured by radiation oncologists and those obtained from the old atlas, mean overlap volumes were 0.75 ± 0.08 and 0.74 ± 0.13 for the right and left breasts, respectively. Twenty cases (ten right breasts and ten left breasts) used to create the new atlas were also reprocessed by this same atlas in order to assess the quality of automatic contouring of the breast when the case was already known to the software. The mean overlap volume in this case was 0.84 ± 0.08 for the right breast and 0.83 ± 0.06 for the left breast. Finally, after automatic contouring of organs at risk by means of the new atlas, the mean overlap volume was 0.87 ± 0.04 for the heart and 0.93 for each lung (±0.05 for the right lung and ± 0.04 for the left lung).ConclusionWorkflow Box™ automatic contouring software, based on our new atlas provides reliable and clinically relevant organs at risk and breast contouring. The contours proposed by the software from the new atlas were better than those obtained with the previous atlas based on 95% isodoses obtained from old treatment plans. This software has therefore become more efficient, justifying its use in routine clinical practice for breast cancer contouring in patients treated in the lateral decubitus position. Investigations are currently underway to develop a fully automated process to ensure reliable, robust and operator-independent contouring and breast cancer treatment dosimetry in the lateral decubitus position. Promising preliminary results have already been obtained.     

Optimal radiotherapy after breast-conserving surgery for early breast cancer: A network meta-analysis of 23,418 patients

PurposeIn order to explore whether partial breast irradiation can replace hypofractionated whole breast irradiation and whether the former two are superior to conventional fractionated whole breast irradiation, we conducted a network meta-analysis based on the data from the latest randomized controlled trials to evaluate the efficacy of these radiotherapy modalities.Material and methodsData from eligible studies were analyzed to determine the published events for ipsilateral breast tumor recurrence, distant metastasis, total deaths, and non-breast cancer-related deaths. In the case of low or high heterogeneity, the fixed-effect or random-effect model was used for statistical analysis respectively. NMA was performed by using the node-splitting model for two-category data among three radiotherapies based on a Bayesian method.ResultsA total of 23,418 patients were included in 16 studies. For ipsilateral breast tumor recurrence, both pairwise (OR=1.9; CI95%: 1.2 -2.8; p<0.05) and indirect (OR=1.7; CI95%: 1.2 -2.4; p<0.05) comparison of three radiotherapies by network meta-analysis showed that conventional fractionated whole breast irradiation was significantly better than partial breast irradiation. Indirect comparison of three radiotherapies by network meta-analysis showed that hypofractionated whole breast irradiation was significantly better than partial breast irradiation (OR=1.6; CI95%: 1.0 -2.5; p<0.05). Network and paired meta-analyses found no significant differences in other endpoints among the three radiotherapies.ConclusionOverall, this network meta-analysis showed that partial breast irradiation was related to the increase of ipsilateral breast tumor recurrence compared with hypofractionated or conventional fractionated whole breast irradiation in patients with early-stage breast cancer.