D. Antoni

Three-Dimensional Cell Culture: A Breakthrough in Vivo

Cell culture is an important tool for biological research. Two-dimensional cell culture has been used for some time now, but growing cells in flat layers on plastic surfaces does not accurately model the in vivo state. As compared to the two-dimensional case, the three-dimensional (3D) cell culture allows biological cells to grow or interact with their surroundings in all three dimensions thanks to an artificial environment. Cells grown in a 3D model have proven to be more physiologically relevant and showed improvements in several studies of biological mechanisms like: cell number monitoring, viability, morphology, proliferation, differentiation, response to stimuli, migration and invasion of tumor cells into surrounding tissues, angiogenesis stimulation and immune system evasion, drug metabolism, gene expression and protein synthesis, general cell function and in vivo relevance. 3D culture models succeed thanks to technological advances, including materials science, cell biology and bioreactor design.

Institutional, Retrospective Analysis of 777 Patients With Brain Metastases: Treatment Outcomes and Diagnosis-Specific Prognostic Factors

PURPOSE To retrospectively evaluate the prognostic factors and survival of a series of 777 patients with brain metastases (BM) from a single institution. METHODS AND MATERIALS Patients were treated with surgery followed by whole-brain radiation therapy (WBRT) or with WBRT alone in 16.3% and 83.7% of the cases, respectively. The patients were RPA (recursive partitioning analysis) class I, II, and III in 11.2%, 69.6%, and 18.4% of the cases, respectively; RPA class II-a, II-b, and II-c in 8.3%, 24.8%, and 66.9% of the cases, respectively; and with GPA (graded prognostic assessment) scores of 0-1.0, 1.5-2.0, 2.5-3.0, and 3.5-4.0 in 35%, 27.5%, 18.2%, and 8.6% of the cases, respectively. RESULTS The median overall survival (OS) times according to RPA class I, II, and III were 20.1, 5.1, and 1.3 months, respectively (P<.0001); according to RPA class II-a, II-b, II-c: 9.1, 8.9, and 4.0 months, respectively (P<.0001); and according to GPA score 0-1.0, 1.5-2.0, 2.5-3.0, and 3.5-4.0: 2.5, 4.4, 9.0, and 19.1 months, respectively (P<.0001). By multivariate analysis, the favorable independent prognostic factors for survival were as follows: for gastrointestinal tumor, a high Karnofsky performance status (KPS) (P=.0003) and an absence of extracranial metastases (ECM) (P=.003); for kidney cancer, few BM (P=.002); for melanoma, few BM (P=.01), an absence of ECM (P=.002), and few ECM (P=.0002); for lung cancer, age (P=.007), a high KPS (P<.0001), an absence of ECM (P<.0001), few ECM and BM (P<.0001 and P=.0006, respectively), and control of the primary tumor (P=.004); and for breast cancer, age (P=.001), a high KPS (P=.007), control of the primary tumor (P=.05), and few ECM and BM (P=.01 and P=.0002, respectively). The triple-negative subtype was a significant unfavorable factor (P=.007). CONCLUSION Prognostic factors varied by pathology. Our analysis confirms the strength of prognostic factors used to determine the GPA score, including the genetic subtype for breast cancer.

Outcomes in Newly Diagnosed Elderly Glioblastoma Patients after Concomitant Temozolomide Administration and Hypofractionated Radiotherapy

This study aimed to analyze the treatment and outcomes of older glioblastoma patients. Forty-four patients older than 70 years of age were referred to the Paul Strauss Center for chemotherapy and radiotherapy. The median age was 75.5 years old (range: 70–84), and the patients included 18 females and 26 males. The median Karnofsky index (KI) was 70%. The Charlson indices varied from 4 to 6. All of the patients underwent surgery. O6-methylguanine–DNA methyltransferase (MGMT) methylation status was determined in 25 patients. All of the patients received radiation therapy. Thirty-eight patients adhered to a hypofractionated radiation therapy schedule and six patients to a normofractionated schedule. Neoadjuvant, concomitant and adjuvant chemotherapy regimens were administered to 12, 35 and 20 patients, respectively. At the time of this analysis, 41 patients had died. The median time to relapse was 6.7 months. Twenty-nine patients relapsed, and 10 patients received chemotherapy upon relapse. The median overall survival (OS) was 7.2 months and the one- and two-year OS rates were 32% and 12%, respectively. In a multivariate analysis, only the Karnofsky index was a prognostic factor. Hypofractionated radiotherapy and chemotherapy with temozolomide are feasible and acceptably tolerated in older patients. However, relevant prognostic factors are needed to optimize treatment proposals.

An institutional retrospective analysis of 93 patients with brain metastases from breast cancer: treatment outcomes, diagnosis-specific prognostic factors.

To evaluate the prognostic factors and indexes of a series of 93 patients with breast cancer and brain metastases (BM) in a single institution. Treatment outcomes were evaluated according to the major prognostic indexes (RPA, BSBM, GPA scores) and breast cancer subtypes. Independent prognostic factors for overall survival (OS) were identified. The median OS values according to GPA 0–1, 1.5–2, 2.5–3 and 3.5–4, were 4.5, 9.5, 14.2 and 19.1 months, respectively (p < 0.0001) and according to genetic subtypes, they were 5, 14.2, 16.5 and 17.1 months for basal-like, luminal A and B and HER, respectively (p = 0.04). Using multivariate analysis, we established a new grading system using the six factors that were identified as indicators of longer survival: age under 60 (p = 0.001), high KPS (p = 0.007), primary tumor control (p = 0.05), low number of extracranial metastases and BM (p = 0.01 and 0.0002, respectively) and triple negative subtype (p = 0.002). Three groups with significantly different median survival times were identified: 4.1, 9.5 and 26.3 months, respectively (p < 0.0001). Our new grading system shows that prognostic indexes could be improved by using more levels of classification and confirms the strength of biological prognostic factors.

Chemoradiotherapy of locally advanced nonsmall cell lung cancer: state of the art and perspectives.

Purpose of review The treatment of locally advanced nonsmall cell lung cancer (NSCLC) is becoming a significant challenge because of a growing proportion of patients with unresectable or potentially eligible for surgery after a multimodality treatment, stage II to III disease. Despite a multimodality approach consisting in concurrent chemoradiotherapy, the prognosis remains poor. Recent findings Different strategies, including induction and consolidation chemotherapy, chemotherapy regimens, fractionation and radiation doses have been evaluated in phase II and III trials, as well as new therapeutic approaches such as immunotherapy. For patients with resectable stage III disease the optimal strategy remains unclear. The American Society for Radiation and Clinical Oncology and the European Society for Medical Oncology published recent guidelines in 2015. Summary Concurrent chemoradiotherapy improves overall survival compared with sequential chemotherapy followed by radiation. Adding induction or consolidation chemotherapy to chemoradiotherapy does not appear to improve the outcome. Chemotherapy based on cisplatin combined with radiation is recommended in stage III NSCLC. The standard dose and fractionation of radiotherapy are 60 Gy, one daily fraction of 2 Gy over 6 weeks. Targeted therapies and immunotherapy may improve the management of locally advanced NSCLC in the future.

Radiothérapie encéphalique en totalité des métastases cérébrales : intérêts et controverses dans le cadre d’un référentiel

Whole brain radiation therapy is the angular stone of the brain metastasis radiation therapy. This treatment allows reaching two goals, potentially curative for in place metastasis and prophylactic in the rest of brain tissue. However, these two advantages can be disputed and in light of the same data opposite conclusions could be drawn.

Place de la radiothérapie panencéphalique dans les métastases cérébrales

Brain metastases are the leading cause of intracranial malignancy and a major cause of mortality and morbidity. From 20 to 40% of cancer patients develop brain metastases. The irradiation of the whole brain remains the most commonly undertaken treatment, but should be discussed in relation to other therapeutic alternatives such as stereotactic radiotherapy or the use of new chemotherapy drugs. Its use according to pathology should be discussed. It can lead to a long-term neurocognitive toxicity that should be evaluated more precisely. This literature review aims to highlight the role of whole-brain radiotherapy used alone or in combination with other treatments.

Treatment that follows guidelines closely dramatically improves overall survival of patients with anal canal and margin cancers

BACKGROUND To assess relevance of ESMO-ESSO-ESTRO treatment guidelines in a retrospective analysis of patients with anal canal or anal margin cancers. MATERIAL AND METHODS 155 patients were separated into standard treatment group (STG), treated according to or closely the guidelines, and an altered treatment group (ATG). RESULTS The median follow-up time was 50.7 months. In the STG, the 5- and 10-year LR-DFS rates were 75.2% and 72.7%; in the ATG, they were 66.8% and 61.2%, respectively. In the STG, the 5- and 10-year OS rates were 81.8% and 68%; in the ATG, they were 63.3% and 49.5%, respectively (p=0.037). In the multivariate analysis, favorable prognostic factors for OS included the standard treatment, age <60, tumor 50.4Gy. CONCLUSION This study identifies the superiority of treatment according to standard guidelines compared to altered treatment. Our results corroborate the guidelines.

The role of whole brain radiation therapy for brain metastases

Brain metastases are the leading cause of intracranial malignancy and a major cause of mortality and morbidity. From 20 to 40% of cancer patients develop brain metastases. The irradiation of the whole brain remains the most commonly undertaken treatment, but should be discussed in relation to other therapeutic alternatives such as stereotactic radiotherapy or the use of new chemotherapy drugs. Its use according to pathology should be discussed. It can lead to a long-term neurocognitive toxicity that should be evaluated more precisely. This literature review aims to highlight the role of whole-brain radiotherapy used alone or in combination with other treatments.

Comorbidities in the management of patients with lung cancer

Lung cancer represents a major public health issue worldwide. Unfortunately, more than half of them are diagnosed at an advanced stage. Moreover, even if diagnosed early, diagnosis procedures and treatment can be difficult due to the frequent comorbidities observed in these patients. Some of these comorbidities have a common major risk factor, i.e. smoking, whereas others are unrelated to smoking but frequently observed in the general population. These comorbidities must be carefully assessed before any diagnostic and/or therapeutic decisions are made regarding the lung cancer. For example, in a patient with severe emphysema or with diffuse lung fibrosis, transthoracic needle biopsy can be contraindicated, meaning that in some instances a precise diagnosis cannot be obtained; in a patient with chronic obstructive pulmonary disease, surgery may be impossible or should be preceded by intensive rehabilitation; patients with interstitial lung disease are at risk of radiation pneumonitis and should not receive drugs which can worsen the respiratory insufficiency. Patients who belong to what are called “special populations”, e.g. elderly or HIV infected, should be treated specifically, especially regarding systemic treatment. Last but not least, psychosocial factors are of great importance and can vary from one country to another according to health insurance coverage. Comorbidities are frequent in patients with lung cancer and impact on their diagnostic and therapeutic management http://ow.ly/7ixJ307cpbL