Regorafenib-avelumab combination in patients with biliary tract cancer (REGOMUNE): a single-arm, open-label, phase II trial.

BACKGROUND: Regorafenib has shown substantial clinical activity in patients with advanced biliary tract cancers (BTCs). Preclinical data suggested that this drug modulates antitumour immunity and is synergistic with immune checkpoint inhibition. PATIENTS AND METHODS: This is a single-arm, multicentric phase II trial. Regorafenib was given 3 weeks/4, 160 mg quaque die (once a day) (QD); avelumab 10 mg/kg IV was given every two weeks, beginning at C1D15 until progression or unacceptable toxicity. The primary end-point was the confirmed objective response rate under treatment, as per Response Evaluation Criteria in Solid Tumours 1.1. The secondary end-points included the following: 1-year non-progression rate; progression-free survival (PFS) and overall survival; safety and biomarkers studies performed on sequential tumour samples obtained at baseline and at cycle 2 day 1. RESULTS: Thirty-four patients were enrolled in four centres. Twenty-nine patients were assessable for efficacy after central radiological review. The best response was partial response for four patients (13.8%), stable disease for 11 patients (37.9%) and progressive disease for 14 patients (48.3%). The median PFS and overall survival were 2.5 months (95% confidence interval [CI] [1.9-5.5]) and 11.9 months (95%CI [6.2-NA]) respectively. The most common grade 3 or 4 clinical adverse events related to treatment were hypertension (17.6%), fatigue (14.7%) and maculopapular rash (11.8%). High baseline levels of programmed cell death ligand 1 and of indoleamine 2, 3-dioxygénase expression were associated with improved outcomes. CONCLUSIONS: Regorafenib combined with avelumab has antitumour activity in a subset of heavily pretreated biliary tract cancer population. Further investigations are needed in patients selected based on tumour microenvironment features. CLINICAL TRIAL REGISTRATION: NCT03475953.

Mature tertiary lymphoid structures predict immune checkpoint inhibitor efficacy in solid tumors independently of PD-L1 expression.

Only a minority of patients derive long-term clinical benefit from anti-PD1/PD-L1 monoclonal antibodies. The presence of tertiary lymphoid structures (TLS) has been associated with improved survival in several tumor types. Here, using a large-scale retrospective analysis of three independent cohorts of cancer patients treated with anti-PD1/PD-L1 antibodies, we showed that the presence of mature TLS was associated with improved objective response rate, progression-free survival, and overall survival independently of PD-L1 expression status and CD8+ T-cell density. These results pave the way for using TLS detection to select patients who are more likely to benefit from immune checkpoint blockade.

Prospective evaluation of an anti-cancer drugs management programme in a dedicated oral therapy center (DICTO programme).

Oral therapies have highly modified cancer patient management and changed hospital practises. We introduce a specific Oral Therapy Centre and retrospectively review information prospectively recorded by co-ordination nurses (CNs) (the DICTO programme). We describe the roles played by CNs in the management of oral cancer therapies at Limoges Dupuytren Hospital between May 2015 and June 2018. All cancers, irrespective of stage or whether oral general chemotherapy or targeted therapy was prescribed, are included. We followed up 287 patients of median age 67 years (range 26-89 years). Of these, 76% had metastases and 44% were on first-line therapy. The vast majority (88%) of their first CN contacts occurred just after physician consultation and lasted an average of 60 min. As part of follow-up, the CNs made 2719 calls (average 10 min) to patients to educate them and to verify compliance and drug tolerance. They also received 833 calls from patients (70%) or their relatives or health professionals (30%) seeking advice on management of side effects. In addition to the initial appointments, 1069 non-scheduled follow-up visits were made to assess side effects (49.2%). The CNs devoted 5 h to each patient over 3 months of treatment (i.e. 25 min/day) and, also organised scheduled hospitalisations in the department of oncology for 51% of patients. We show the interest and real-life work in a specific oral therapy centre within oncology department with the role of CNs to facilitate the global health care of the patients.

Basic Knowledge in Soft Tissue Sarcoma.

Sarcoma is rare and heterogenous with various subtypes having a different prognostic. Desmoid is a tumour with a local aggressiveness; GIST with KIT mutation responds massively to target treatment as IMATINIB, whereas soft tissue sarcoma and leiomyosarcoma are very aggressive with poor response to systemic therapies. Interventional radiology plays an important role in the diagnosis of sarcomas with image-guided percutaneous core needle biopsy being the most commonly used biopsy technique in the diagnosis of sarcomas. Biopsy access routes discussed with the surgeon, and skin access is tattooed. Surgery is a mainstay of sarcoma treatment; the resection can be large. Indeed, resection objective is R0 because quality of surgical margins impacts local control and survival. Radiotherapy is possible in neoadjuvant or in adjuvant treatment to improve local control rate. Recently radiotherapy enhancer injected percutaneously in soft tissue sarcoma has proven benefit in increasing the rate of R0 complete surgical resection. Several studies showed better local control rate linked with post-operative radiotherapy. In patients affected by oligometastatic disease, complete surgical resection of all metastatic sites is in fact considered the primary treatment because complete remission is critical for cure. The decision making to use local therapies is complex, depends upon diverse presentations and histologies, and should always be taken in a multidisciplinary discussion. Today, percutaneous image-guided treatments with ablation technologies (radiofrequency ablation, cryotherapy, microwaves ablation) provide high rate of durable local control for small-sized malignant deposit in many organs including lung, liver and bones. Sarcoma must be managed by multimodality treatment in expert reference centres. Such management has a considerable impact on the prognosis.

Outcome of Patients with Soft-Tissue Sarcomas: An Age-Specific Conditional Survival Analysis.

BACKGROUND: Soft-tissue sarcomas (STSs) are a group of rare cancers that can occur at any age. Prognostic outcomes of patients with STS are usually established at the time of the patient's initial disease presentation. Conditional survival affords a dynamic prediction of prognosis for patients surviving a given period after diagnosis. Estimates of conditional survival can provide crucial prognostic information for patients and caregivers, guide subsequent cancer follow-up schedules, and impact decisions regarding management. This study aims to estimate conditional survival and prognostic factors in patients with STS according to age at diagnosis (≤75 years and ≥75 years). SUBJECTS, MATERIALS, AND METHODS: A total of 6,043 patients with nonmetastatic STS at first diagnosis who underwent complete surgical resection (R0 or R1) were assessed. Cox proportional hazards regression was used to establish prognostic factors of conditional metastasis-free survival and overall survival at 1, 2, and 5 years after diagnosis. RESULTS: Elderly patients have more adverse prognostic features at presentation and tend to receive less aggressive treatment than do younger patients. However, at baseline as well as at each conditional survival time point, the 5-year estimated probability of metastatic relapse decreases in both young and elderly patients and is almost identical in both groups at 2 years and 5 years after initial diagnosis. Prognostic factors for metastatic relapse and death change as patient survival time increases in both young and elderly patients. Grade, the strongest prognostic factor for metastatic relapse and death at baseline, is no longer predictive of metastatic relapse in patients surviving 5 years after initial diagnosis. Leiomyosarcoma is the histological subtype associated with the highest risk of metastatic relapse and death in young patients surviving 5 years after initial diagnosis. The positive impact on the outcome of peri-operative treatments tends to decrease and disappears in patients surviving 5 years after initial diagnosis. CONCLUSION: Conditional survival estimates show clinically relevant variations according to time since first diagnosis in both young and elderly patients with STS. These results can help STS survivors adjust their view of the future and STS care providers plan patient follow-up. IMPLICATIONS FOR PRACTICE: For patients with sarcoma who are followed up years after being treated for their disease, a common scenario is for the patient and caregivers to ask practitioners what the longer-term prognosis may be. The question posed to practitioners may be, "Doc, am I now cured? It's been 5 years since we finished treatment." Survival probability changes for patients who survive a given period of time after diagnosis, and their prognosis is more accurately described using conditional survival. By analyzing more than 6,000 sarcoma patients, an overall improvement was found in the risk of relapse as patients conditionally survive. Prognostic factors for metastatic relapse and death change as patient survival time increases in both young and elderly patients.

Newer therapeutic strategies for soft-tissue sarcomas.

Metastatic soft-tissue sarcoma (STS), a devastating disease, has a median overall survival of only 12-18 months. Until recently, therapeutic options were limited and relied primarily on the use of anthracycline-based chemotherapy. Over the past two decades, improvement in the knowledge of the biology of STS has allowed the investigation of new therapeutic strategies including new cytotoxic agents, epigenetic drugs, specific targeted therapies, and immunotherapeutic treatments.

Lobular Breast Carcinoma Metastasis to the Thyroid Gland: Case Report and Literature Review.

Metastasis from primary cancer to the thyroid is uncommon in breast cancer. Here we present a case of lobular breast carcinoma that metastasized to the thyroid. A 54-year-old woman without symptoms was admitted to our institution for staging of the lymph node above the left clavicle. An 18F-fluoro-deoxy-D-glucose positron emission tomography scan was performed for staging, and low uptakes were observed in the left supraclavicular and cervical lymph nodes. High uptake was seen in the posterior and lower left lobe of the thyroid. Histologic findings indicated lobular breast carcinoma (positive GATA3, loss of E-cadherin expression) metastatic to the thyroid with a luminal profile. Immunohistochemical analysis was negative for primary thyroid or parathyroid carcinoma. To our knowledge, this is the first report of a patient presenting a metastatic invasive lobular carcinoma in the thyroid and lymph nodes without a prior diagnosis of breast cancer.