[Medical oncological treatment of colorectal cancer in the elderly]. / Traitement oncologique médical du cancer colorectal chez la personne âgée.

Medical treatment with chemotherapy is discussed in several situations in the treatment of colon cancer. In the adjuvant setting, chemotherapy with 5FU±oxaliplatin for six months should be considered in the case of lymph node involvement. In the metastatic setting, several protocols exist. The choice of treatments should be based on the expected objectives in terms of response and survival gain, but also of tolerance and quality of life for the patient. A thorough oncogeriatric assessment helps to better define the therapeutic programme. The continuation of geriatric follow-up throughout the treatment process shows a benefit for the patient in terms of quality of life and tolerance of treatments.

Complete response in anaplastic lymphoma kinase-rearranged oncocytic thyroid cancer: A case report and review of literature.

BACKGROUND: Oncocytic carcinoma of the thyroid is a rare disease, characterized by a poor prognosis and low response rate to radioiodine therapy. Crizotinib is a specific anaplastic lymphoma kinase (ALK) inhibitor, which was initially developed in non-small cell lung cancer. Other solid tumors harboring a translocation in ALK have been described, such as renal carcinoma, thyroid, colorectal, ovarian cancers, and spitzoid melanoma. The research of ALK rearrangements in thyroid tumor is a promising therapeutic track, and treatments need to be explored. CASE SUMMARY: We report the case of a 76-year-old woman with a history of multinodular goiter, who was hospitalized for impairment of her general condition. She was diagnosed with metastatic oncocytic thyroid cancer. Synchrone metastases were found: Multiple mediastinal lymphadenopathies, lytic bone lesions and bilateral mammary lumps. Fluorescence in situ hybridization analysis revealed an ALK rearrangement in 61% of cells. No other mutation was found. A tumor board discussion based on molecular characteristics of the tumor suggested initiating a daily treatment by crizotinib, a specific ALK inhibitor. A positron emission tomography scan performed 4 mo after the initiation of crizotinib showed a complete metabolic response. CONCLUSION: This case highlights an unexpected efficacy of crizotinib in an ALK-rearranged thyroid tumor, and the need of further assessments.

Immunotherapy and metastatic colorectal cancers with microsatellite instability or mismatch repair deficiency.

Microsatellite instability (MSI) is a molecular indicator of defective DNA mismatch repair (dMMR) and is observed in approximately 5% of metastatic colorectal cancers (mCRC). MSI is a major predictive biomarker for the efficacy of immune checkpoint inhibitors (ICKi) amongst mCRC patients. After summarizing the literature about the efficacy of conventional cytotoxic regimens, we will highlight studies that have demonstrated the clinical activity of ICKi for patients with chemoresistant MSI/dMMR mCRC. Then we will focus on ongoing clinical trials and emerging challenges for the treatment of patients with MSI/dMMR mCRC.

Evaluation of short-term efficacy of extraspinal cementoplasty for bone metastasis: A monocenter study of 31 patients.

OBJECTIVE: To study the effect on pain of per-cutaneous cementoplasty for painful extraspinal bone metastasis. METHOD: 43 patients with extraspinal bone metastasis were included between April 2006 and October 2014 in this retrospective monocenter study. The primary endpoint was pain level measured on a 0-10 numeric rating scale at week 1 after cementoplasty as compared with pre-cementoplasty. Secondary endpoints were long-term pain level and impact on quality of life and disability. RESULTS: Mean pain score was 4.2 (SD ±3.6) before cementoplasty and 1.09 (SD ±2.4) at week 1 (p = 0.005) (n = 31 patients). At 22 months after cementoplasty, quality of life and disability improved (according to the patient global assessment) for 47.6% and 52.2% of patients (n = 21patients). We did not find a predictor of good response. Cement leakage was the most common adverse event. CONCLUSION: Percutaneous cementoplasty of extraspinal bone metastasis is a rapidly efficient treatment with few adverse events. Its efficacy persists over time, with a benefit for disability and quality of life. Although this technique is only palliative, it should be considered in this situation.

Polymerase proofreading domain mutations: New opportunities for immunotherapy in hypermutated colorectal cancer beyond MMR deficiency.

Immune checkpoint inhibition is a new therapeutic strategy that has shown promising efficacy in many cancer types. Significant activity associated with mismatch repair (MMR) deficiency has been observed in hypermutated, microsatellite unstable (MSI) metastatic colorectal cancer (CRC). Beyond deficient-MMR tumors, somatic or germline DNA polymerase D1 (POLD1) or DNA polymerase E (POLE) alterations cause a hypermutated phenotype in CRC. This recently identified and rare subgroup of proficient-MMR tumors may also benefit from immunotherapy. In this review, we provide a comprehensive overview of recent data on CRC tumors harboring POLD1 or POLE mutations, with a focus on their molecular, histological, and clinical features. We also examine the evidence supporting the development of immune checkpoint inhibitors in this specific subgroup of CRC patients.

[De novo cancer after solid organ transplantation: Epidemiology, prognosis and management]. / Cancers solides après transplantation d'organe : épidémiologie, pronostic et spécificités de prise en charge.

The risk of cancer after solid organ transplantation is increased by 2.6 compared to overall population. Cancer is currently the third leading cause of death in solid organ transplanted patients, making screening and early management of de novo cancers a major challenge. This increased risk of cancer in this population results from the combination of known environmental risk factors of cancer, comorbidities of transplanted patients, and exposure to chronic immunosuppression. The prognosis of cancer in these patients seems poorer as compared to other cancer patients owing to their comorbidities, the immunosuppression and patient's poorer tolerance to oncologic treatment. Moreover, interactions between immunosuppressive agents and antitumor therapies must be taken into account in the therapeutic strategy. Better knowledge of the specificities of solid organ transplanted patients with de novo cancer is required to improve cancer care in this patient population. This article aims to review the current data available on de novo cancers in solid organ transplanted patients, with a focus on epidemiology, risks factors of de novo cancers, impact of immunosuppressive drugs and oncologic prognosis.

First-line antiangiogenics for metastatic renal cell carcinoma: A systematic review and network meta-analysis.

BACKGROUND: Sunitinib, pazopanib, sorafenib, axitinib and bevacizumab are the five recommended antiangiogenic agents in first-line therapy for metastatic renal cell carcinoma (mRCC). Because these drugs underwent simultaneous clinical development, no direct efficacy and safety comparison was ever conducted, thus preventing optimal therapy choices. METHODS: We performed a traditional and network meta-analysis to evaluate the efficacy and safety of mRCC-recommended first-line antiangiogenic agents. After a systematic review of Medline and Embase up to July 2014, we identified randomized clinical trials (RCTs) evaluating the outcomes of mRCC patients treated with sunitinib, pazopanib, sorafenib, axitinib and bevacizumab as first-line treatment. Endpoints of interest were response rate, progression-free survival (PFS), overall survival (OS), and safety. RESULTS: We screened 769 abstracts and included nine RCTs with a total of 4282 patients. In the weighted pooled analysis, first-line antiangiogenic agents showed significant improvement in PFS (HR=0.6; 95% IC, 0.51-0.72) and OS (HR=0.85; 95% IC, 0.78-0.93) compared to control (placebo or interferon-alpha2a (INF)). Network meta-analysis showed no significant differences among antiangiogenic drugs in 6-month PFS, 1-year OS, disease control rate and drug-related safety for all-grade hypertension, diarrhea, weight-loss, nausea or anorexia. However, pazopanib showed a lower incidence of fatigue, anemia and hand foot skin reaction. CONCLUSIONS: This meta-analysis confirms the benefits of first-line antiangiogenic therapy in mRCC, with an improvement in OS. Sunitinib, pazopanib, axitinib and bevacizumab + INF offer similar efficacy but different safety profiles which can help clinicians to better personalize treatment decisions in patients with mRCC.

Balanced Translocations Disrupting SMARCB1 Are Hallmark Recurrent Genetic Alterations in Renal Medullary Carcinomas.

BACKGROUND: Renal medullary carcinoma (RMC) is a rare and highly aggressive neoplasm that most often occurs in the setting of sickle cell trait or sickle cell disease (SCD). Most patients present with metastatic disease resistant to conventional chemotherapy, and therefore there is an urgent need for molecular insight to propose new therapies. OBJECTIVE: To determine the molecular alterations and oncogenic pathways that drive RMC development. DESIGN, SETTING, AND PARTICIPANTS: A series of five frozen samples of patients with RMC was investigated by means of gene expression profiling, array comparative genomic hybridization, and RNA and whole exome sequencing (WES). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: RNA and DNA sequencing read data were analyzed to detect gene fusions and somatic mutations. Gene fusions mutations were validated by real-time polymerase chain reaction and fluorescence in situ hybridization. Gene expression profiling was analyzed by unsupervised hierarchical clustering and Gene Set Enrichment Analysis (Broad Institute, Cambridge, MA, USA). RESULTS AND LIMITATIONS: We observed inactivation of the tumor suppressor gene SMARCB1 in all tumors. In all four cases developed in patients with SCD, we identified an original mechanism of interchromosomal balanced translocations that disrupt the SMARCB1 sequence and thus contribute to its inactivation. Gene expression profiling revealed that RMC shares common oncogenic pathways with pediatric malignant rhabdoid tumors, another tumor subtype characterized by SMARCB1 deficiency. CONCLUSIONS: RMCs are characterized by an original mechanism of interchromosomal balanced translocations that disrupt the SMARCB1 sequence. WES reveals that RMCs show no other recurrent genetic alteration and an overall stable genome, underscoring the oncogenic potency of SMARCB1 inactivation. PATIENT SUMMARY: Our comprehensive molecular study supports a pivotal role of the tumor suppressor gene SMARCB1 in the development of renal medullary carcinoma. The use of therapeutic strategies based on the biologic effects of its inactivation should now open new perspectives for this typically lethal malignancy.