Prognostic factors of the synovial sarcoma of the extremities: imaging does matter.

OBJECTIVES: Synovial sarcomas (SS) of the extremities are rare soft tissue sarcomas that are more common in young adults. We deciphered the imaging phenotype of SS with the aim to determine if imaging could provide an incremental value to currently known prognostic factors (PF)-age and histological grade-to predict long-term overall survival (OS). METHODS: This retrospective multicenter study included consecutive pediatric and adult patients with synovial sarcomas of the extremities from December 2002 to August 2020. Inclusion criteria were (i) a follow-up greater than 5 years and (ii) available pre-therapeutic MRI. A subset analysis included MRI and CT-scan. Clinical, pathological, and imaging variables were collected in all patients. The primary endpoint was to evaluate the association of these variables with OS using univariate and multivariate Cox regressions. RESULTS: Out of 428 patients screened for eligibility, 98 patients (mean age: 37.1 ± 15.2 years) were included (MRI: n = 98/98, CT scan: n = 34/98; 35%). The median OS was 75.25 months (IQR = 55.50-109.12) and thirty-six patients (n = 36/98;37%) died during follow-up. The recurrence rate was 12.2% (n =12/98). SS lesions were mostly grade 2 (57/98; 58%). On MRI, SS had a mean long-axis diameter of 67.5 ± 38.3 mm. On CT scan, 44% (15/34) were calcified. Grade (hazard ratio [HR] = 2.71; 95%CI = 1.30-5.66; p = 0.008), size of the lesions evaluated on MRI (HR = 1.02; 95% CI = 1.01-1.03; p < 0.001), and calcifications on CT scan (HR = 0.10; 95% CI = 0.02-0.50; p = 0.005) were independent PF of OS. CONCLUSIONS: This study demonstrated that imaging biomarkers can be used to predict long-term outcome in patients with SS. Strikingly, the presence of calcifications on CT scan is associated with favorable outcome and provides an incremental value over existing PF such as age, grade, and size. KEY POINTS: • Beyond its diagnostic value, MRI is a pre-operative prognostic tool in synovial sarcomas of the extremities since the size of the lesion is an important prognostic factor. • Calcifications on CT scans are independently and significantly associated with prolonged overall survival.

Single-agent gemcitabine in patients with advanced, pre-treated angiosarcoma: A multicenter, retrospective study.

Gemcitabine has shown clinical activity against angiosarcoma in small series, alone, or combined with taxanes. We aimed to evaluate its activity as a single-agent in a larger series of patients with advanced angiosarcoma. We retrospectively reviewed the electronic medical records of consecutive adult patients with advanced angiosarcoma treated with single-agent gemcitabine at our institutions from January 2010 to January 2021. Response was evaluated according to RECIST 1.1, and toxicity was graded according to NCI-CTC v5.0. 42 patients were identified. 38 patients (90%) had received prior anthracyclines and weekly paclitaxel, and 9 (21%) had received pazopanib. The best tumor response was partial response (PR) in 16 patients (38%), or stable disease (10 patients, 24%). All 8 patients with cardiac angiosarcoma experienced a PR. Median PFS was 5.4 months (95%CI: 3.1-6.5), and median OS was 9.9 months (95%CI: 6.6-13.4). Single-agent gemcitabine has clinically meaningful activity in advanced, heavily pre-treated angiosarcoma.

Safety of direct oral anticoagulants in patients with advanced solid tumors receiving anti-VEGF agents: a retrospective study.

PURPOSE: Kinase inhibitors (KI) and antibodies targeting the VEGF pathway are approved in a broad spectrum of cancers and associated with an increased risk of bleeding and thromboembolic events (TE). The use of direct oral anticoagulants (DOACs) apixaban and rivaroxaban is increasing in cancer patients, but limited data are available for patients receiving anti-VEGF agents. METHODS: To assess safety of DOAC with concomitant anti-VEGF agents, a retrospective chart review of all patients receiving concomitantly DOAC and anti-VEGF agents was performed from 2013 to 2020 in our center. Data on demographics, safety, and time on treatment were collected. Main outcome was safety (bleeding and thromboembolic events). RESULTS: Of 92 patients (median age 66 years (IQR: 59-72)), 40 were treated with KI and 52 with bevacizumab. The most frequent primary tumor sites were colon/rectum (24%), kidney (21%), ovary (13%), lung (11%), soft tissue sarcoma (10%), and thyroid (9%); 2% had brain metastases. Apixaban 5 mg bid (n = 41) or rivaroxaban 20 mg daily (n = 51) were given for TE (65%), atrial fibrillation (32%), or other indications (3%). The median duration of concomitant treatment was 4.8 months (95%CI: 0.7-50.0) with bevacizumab and 11.7 months (95%CI: 0.1-53.8) with KI. Grade ≥ 3 bleeding events occurred in 5 patients (5%): 4 patients receiving bevacizumab (one grade 5 upper digestive tract bleeding and three grade 3 rectal or vaginal hemorrhages) and 1 patient under cabozantinib for kidney cancer with endobronchial metastasis (grade 3 hemoptysis). Grade ≥ 3 TE occurred in 8 patients (9%): 7 patients receiving bevacizumab (including one grade 5 pulmonary embolism), and one patient receiving sunitinib (grade 3 pulmonary embolism). Median time-to-event (bleeding or thrombotic event) was not reached (NR) (95%CI: 76.9-NR) for KI and 86.9 months (95%CI: 42.9-148.0) for bevacizumab. CONCLUSIONS AND RELEVANCE: In our experience, the use of DOAC was safe in selected patients treated with KI, but unclear with bevacizumab. More data are needed to endorse guidelines in this specific group of patients.

Feasibility and long-term outcomes of surgery for primary thoracic synovial sarcoma.

OBJECTIVES: Primary thoracic synovial sarcoma (SS) is a rare, high-grade, malignancy. Involvement of vital organs is frequent and may decrease the benefits of surgical resection. We reviewed our practice at a highly experienced thoracic-surgery centre to assess early- and long-term outcomes after surgery. METHODS: We conducted a retrospective, observational, single-centre study of patients undergoing curative-intent surgery for primary thoracic SS between 1 January 2000 and 31 January 2021 as part of a multidisciplinary management. We assessed demographics, medical history, histopathology and follow-up information. RESULTS: We enrolled 20 patients (13 males) with a median age of 40 years old and a median tumour size of 11 cm. Neoadjuvant chemotherapy was administered to 13 patients. Surgery consisted in extrapleural pneumonectomy (n = 7), extrapleural lobectomy (n = 5), chest wall resection (n = 4) or tumour resection (n = 4). R0 resection was achieved in 16 (80%) patients. Adjuvant therapy was given to 13 patients. 6 patients developed postoperative complications. The median hospital stay was 11.5 days. Overall survival at 2 and 5 years was 51% and 22%, respectively; median overall survival was 25 months and median disease-free survival was 8.5 months. Relapses occurred in 15 patients. By univariate analysis, incomplete resection was the only significant predictor of survival (P = 0.01). CONCLUSIONS: Primary thoracic SS is an aggressive disease. Surgery included in a multimodal treatment may contribute to achieving a good outcome, providing that an R0 resection is obtained. Given the considerable technical challenges of surgery, patient selection and referral to an experienced centre are crucial to minimize morbidity and mortality.

The Ambulatory Medical Assistance (AMA) programme during active-phase treatment in patients with haematological malignancies: A cost-effectiveness analysis.

CONTEXT: The need for patient navigator is growing, and there is a lack of cost evaluation, especially during survivorship. OBJECTIVE: The objective of this study is to evaluate the cost-effectiveness of an Ambulatory Medical Assistance (AMA) programme in patients with haematological malignancies (HM). DESIGN: A cost-effectiveness analysis of the AMA programme was performed compared to a simulated control arm. SETTING: An interventional, single-arm and prospective study was conducted in a French reference haematology-oncology centre between 2016 and 2020. PARTICIPANTS: Adult patients were enrolled with histologically documented malignant haematology, during their active therapy phase, and treated either by intravenous chemotherapy or oral therapy. METHODS: An extrapolation of the effectiveness was derived from a similar nurse monitoring programme (CAPRI study). Cost effectiveness of the programme was evaluated through adverse events of Grade 3 or 4 avoided in different populations. RESULTS: Included patient (n = 797) from the AMA programme were followed during 125 days (IQR: 0-181), and adverse events (Grade 3/4) were observed in 10.1% of patients versus 13.4% in the simulated control arm. The overall cost of AE avoided was estimated to €81,113, leading to an ICER of €864. CONCLUSION: The AMA programme was shown to be cost-effective compared to a simulated control arm with no intervention.

Safety and Efficacy of Bevacizumab in Cancer Patients with Inflammatory Bowel Disease.

BACKGROUND: The safety of bevacizumab in combination with chemotherapy in patients with inflammatory bowel disease (IBD) and digestive and nondigestive cancers is poorly documented. METHODS: We retrospectively evaluated patient records of all adult cancer patients with IBD at our institution from April 2007 to May 2016 with an update in November 2019. RESULTS: Twenty-seven patients with a history of IBD (Crohn's disease, n = 22; ulcerative colitis, n = 5) who were treated with bevacizumab and chemotherapy for metastatic solid tumors were identified. At the time of advanced cancer diagnosis, 18 patients had quiescent IBD, whereas 9 patients had moderately active IBD. Among those with moderately active IBD, five had received corticosteroids less than six months prior to cancer diagnosis and one had received infliximab. The treated cancers were colorectal cancer (n = 13), small bowel cancer (n = 4), non-small cell lung cancer (n = 3), breast cancer (n = 3), and other cancers (n = 4). Patients received bevacizumab in combination with chemotherapy and/or as maintenance for a median of 6.7 months. Grade 2 or higher bevacizumab-related complications were proteinuria in two patients and hypertension, diarrhea, rectal bleeding, and intestinal perforation in one patient each. No clinical IBD flares were observed during bevacizumab treatment. CONCLUSION: Bevacizumab combined with chemotherapy is safe in cancer patients with moderately active or quiescent IBD.

Digital remote monitoring plus usual care versus usual care in patients treated with oral anticancer agents: the randomized phase 3 CAPRI trial.

Strategies that individualize the care of cancer patients receiving oral anticancer agents offer opportunities to improve treatment adherence and patient care. However, the impact of digital remote monitoring systems in this setting has not been evaluated. Here, we report the results of a phase 3 trial (CAPRI, NCT02828462) to assess the impact of a nurse navigator-led program on treatment delivery for patients with metastatic cancer. Patients receiving approved oral anticancer agents were randomized (1:1) to an intervention combining a nurse navigator-led follow-up system and a web portal-smartphone application on top of usual care, or to usual symptom monitoring at the discretion of the treating oncologist, for a duration of 6 months. The primary objective included optimization of the treatment dose. Secondary objectives were grade ≥3 toxicities, patient experience, rates and duration of hospitalization, response and survival, and quality of life. In 559 evaluable patients the relative dose intensity was higher in the experimental arm (93.4% versus 89.4%, P = 0.04). The intervention improved the patient experience (Patient Assessment of Chronic Illness Care score, 2.94 versus 2.67, P = 0.01), reduced the days of hospitalization (2.82 versus 4.44 days, P = 0.02), and decreased treatment-related grade ≥3 toxicities (27.6% versus 36.9%, P = 0.02). These findings show that patient-centered care through remote monitoring of symptoms and treatment may improve patient outcomes and experience.

Outcomes of Patients With Active Cancer and COVID-19 in the Intensive-Care Unit: A Multicenter Ambispective Study.

Background: Several studies report an increased susceptibility to SARS-CoV-2 infection in cancer patients. However, data in the intensive care unit (ICU) are scarce. Research Question: We aimed to investigate the association between active cancer and mortality among patients requiring organ support in the ICU. Study Design and Methods: In this ambispective study encompassing 17 hospitals in France, we included all adult active cancer patients with SARS-CoV-2 infection requiring organ support and admitted in ICU. For each cancer patient, we included 3 non cancer patients as controls. Patients were matched at the same ratio using the inverse probability weighting approach based on a propensity score assessing the probability of cancer at admission. Mortality at day 60 after ICU admission was compared between cancer patients and non-cancer patients using primary logistic regression analysis and secondary multivariable analyses. Results: Between March 12, 2020 and March 8, 2021, 2608 patients were admitted with SARS-CoV-2 infection in our study, accounting for 2.8% of the total population of patients with SARS-CoV-2 admitted in all French ICUs within the same period. Among them, 105 (n=4%) presented with cancer (51 patients had hematological malignancy and 54 patients had solid tumors). 409 of 420 patients were included in the propensity score matching process, of whom 307 patients in the non-cancer group and 102 patients in the cancer group. 145 patients (35%) died in the ICU at day 60, 59 (56%) with cancer and 86 (27%) without cancer. In the primary logistic regression analysis, the odds ratio for death associated to cancer was 2.3 (95%CI 1.24 - 4.28, p=0.0082) higher for cancer patients than for a non-cancer patient at ICU admission. Exploratory multivariable analyses showed that solid tumor (OR: 2.344 (0.87-6.31), p=0.062) and hematological malignancies (OR: 4.144 (1.24-13.83), p=0.062) were independently associated with mortality. Interpretation: Patients with cancer and requiring ICU admission for SARS-CoV-2 infection had an increased mortality, hematological malignancy harboring the higher risk in comparison to solid tumors.

Exploratory analysis of tumor imaging in a Phase 2 trial with cabozantinib in gastrointestinal stromal tumor: lessons learned from study EORTC STBSG 1317 'CaboGIST'.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are malignant mesenchymal tumors arising in the gastrointestinal tract. Their systemic treatment is based on the use of tyrosine kinase inhibitors (TKIs) with imatinib, sunitinib, and regorafenib being the preferred agents. Assessment of tumor response to TKI treatment in GISTs is traditionally done according the Response Evaluation Criteria in Solid Tumors (RECIST), while Choi criteria have also been proposed as alternative tool assessing both volumetric and density changes on computer tomography (CT) scans. EORTC STBSG 1317 'CaboGIST' was a single-arm prospective Phase 2 trial which met its primary endpoint, as 60% of patients previously treated with imatinib and sunitinib were progression-free at 12 weeks (95% CI 45-74%) based on local RECIST assessment. MATERIALS AND METHODS: We report here an exploratory analysis of local versus central RECIST version 1.1 assessment and a comparison of RECIST version 1.1 versus Choi criteria. RESULTS: Comparisons between local and central RECIST version 1.1 at week 12 revealed discrepancies in 17/43 evaluable cases (39.5%). When comparing Choi with local and central RECIST version 1.1, discrepancies were observed in 27/43 (62.8%) and 21/43 (48.8%) cases, respectively. A total of 68% of evaluable patients were progression-free and alive at week 12 based on local RECIST, 84% according to central RECIST analysis and 81% when applying Choi criteria. Central assessment upgraded the treatment response both with RECIST version 1.1 and Choi. CONCLUSIONS: The results of this exploratory analysis support the conclusion that cabozantinib is active in patients with metastatic or recurrent GIST after treatment with imatinib and sunitinib and confirm once again the limitations of RECIST to capture response to TKI in GIST, and the importance to include density changes in the response evaluation in this setting. Clinical trial number: EORTC 1317, NCT02216578.

Lack of Prognostic Value of CTNNB1 Mutation Profile in Desmoid-Type Fibromatosis.

PURPOSE: This prospective nationwide cohort study aimed to investigate desmoid-type fibromatosis (DF) outcomes, focusing on the prognostic value of CTNNB1 mutations. EXPERIMENTAL DESIGN: ALTITUDES (NCT02867033) was a nationwide prospective cohort study of DF diagnosed between January 2016 and December 2020. At diagnosis, CTNNB1 molecular alterations were identified using next-generation sequencing or Sanger sequencing. The primary endpoint was event-free survival (EFS; progression, relapse, or death). We enrolled 628 patients managed by active surveillance, surgical resection, or systemic treatment as first-line therapy. RESULTS: Overall, 516 (82.2%) patients [368 females (71.3%), median age 40.3 years (range, 1-89)] were eligible for analysis. In 435 (84.3%) cases, there was one CTNNB1 molecular alteration: p.T41A, p.S45F, or p.S45P. The first-line management was active surveillance in 352 (68.2%), surgical resection in 120 (23.3%), and systemic treatments in 44 (8.5%) patients. CTNNB1 mutation distribution was similar across the three therapeutic groups. The median follow-up period was 24.7 (range, 0.4-59.7) months. The estimated 3-year EFS rate was 66.2% [95% confidence interval (CI), 60.5%-71.2%]. DF harboring p.S45F was significantly associated with male sex (P = 0.03), non-abdominal wall sites (P = 0.05), pain (P = 0.007), and large tumor size (P = 0.025). CTNNB1 p.S45F mutation was not significantly associated with EFS, either in univariate (HR, 1.06; 95% CI, 0.65-1.73; P = 0.81) or in multivariate analysis (HR, 0.91; 95% CI, 0.55-1.49; P = 0.71). CONCLUSIONS: We found that CTNNB1 mutation profile was associated with unfavorable prognostic factors but was not a prognostic factor for EFS. See related commentary by Greene and Van Tine, p. 3911.

Inoperable scalp cutaneous angiosarcoma: Complete response after definitive external beam radiation therapy - brachytherapy association.

Effective treatments are scarce in non-operable scalp cutaneous angiosarcoma patients. Curative-intent definitive sequential IMRT and plesiobrachytherapy allowed complete response with limited side effect in two elder patients. This could represent a non-invasive therapeutic option for patients with locally advanced presentation.

Immunologic constant of rejection signature is prognostic in soft-tissue sarcoma and refines the CINSARC signature.

BACKGROUND: Soft-tissue sarcomas (STSs) are heterogeneous and aggressive tumors, with high metastatic risk. The immunologic constant of rejection (ICR) 20-gene signature is a signature of cytotoxic immune response. We hypothesized that ICR might improve the prognostic assessment of early-stage STS. METHODS: We retrospectively applied ICR to 1455 non-metastatic STS and searched for correlations between ICR classes and clinicopathological and biological variables, including metastasis-free survival (MFS). RESULTS: Thirty-four per cent of tumors were classified as ICR1, 27% ICR2, 24% ICR3, and 15% ICR4. These classes were associated with patients' age, pathological type, and tumor depth, and an enrichment from ICR1 to ICR4 of quantitative/qualitative scores of immune response. ICR1 class was associated with a 59% increased risk of metastatic relapse when compared with ICR2-4 class. In multivariate analysis, ICR classification remained associated with MFS, as well as pathological type and Complexity Index in Sarcomas (CINSARC) classification, suggesting independent prognostic value. A prognostic clinicogenomic model, including the three variables, was built in a learning set (n=339) and validated in an independent set (n=339), showing greater prognostic precision than each variable alone or in doublet. Finally, connectivity mapping analysis identified drug classes potentially able to reverse the expression profile of poor-prognosis tumors, such as chemotherapy and targeted therapies. CONCLUSION: ICR signature is independently associated with postoperative MFS in early-stage STS, independently from other prognostic features, including CINSARC. We built a robust prognostic clinicogenomic model integrating ICR, CINSARC, and pathological type, and suggested differential vulnerability of each prognostic group to different systemic therapies.

Adjuvant Imatinib in Patients with GIST Harboring Exon 9 KIT Mutations: Results from a Multi-institutional European Retrospective Study.

PURPOSE: The effect of high-dose imatinib (800 mg/day) on survival in the adjuvant treatment of patients with resected KIT exon 9-mutated gastrointestinal stromal tumors (GIST) is not established. Here, the association of dose and other clinicopathologic variables with survival was evaluated in a large multi-institutional European cohort. EXPERIMENTAL DESIGN: Data from 185 patients were retrospectively collected in 23 European GIST reference centers. Propensity score matching (PSM) and inverse-probability of treatment weighting (IPTW) were used to account for confounders. Univariate and multivariate unweighted and weighted Cox proportional hazard regression models were estimated for relapse-free survival (RFS), modified-RFS (mRFS) and imatinib failure-free survival (IFFS). Univariate Cox models were estimated for overall survival. RESULTS: Of the 185 patients, 131 (70.8%) received a starting dose of 400 mg/d and the remaining 54 (29.2%) a dose of 800 mg/d. Baseline characteristics were partially unbalanced, suggesting a potential selection bias. PSM and IPTW analyses showed no advantage of imatinib 800 mg/d. In the weighted multivariate Cox models, high-dose imatinib was not associated with the survival outcomes [RFS: hazard ratio (HR), 1.24; 95% confidence interval (CI), 0.79-1.94; mRFS: HR, 1.69; 95% CI, 0.92-3.10; IFFS: HR, 1.35; 95% CI, 0.79-2.28]. The variables consistently associated with worse survival outcomes were high mitotic index and nongastric tumor location. CONCLUSIONS: In this retrospective series of patients with KIT exon 9-mutated GIST treated with adjuvant imatinib, a daily dose of 800 mg versus 400 mg did not show better results in terms of survival outcomes. Prospective evaluation of the more appropriate adjuvant treatment in this setting is warranted.

Extended Anticoagulant Treatment with Full- or Reduced-Dose Apixaban in Patients with Cancer-Associated Venous Thromboembolism: Rationale and Design of the API-CAT Study.

Cancer-associated thrombosis (CT) is associated with a high risk of recurrent venous thromboembolic (VTE) events that require extended anticoagulation in patients with active cancer, putting them at risk of bleeding. The aim of the API-CAT study (NCT03692065) is to assess whether a reduced-dose regimen of apixaban (2.5 mg twice daily [bid]) is noninferior to a full-dose regimen of apixaban (5 mg bid) for the prevention of recurrent VTE in patients with active cancer who have completed ≥6 months of anticoagulant therapy for a documented index event of proximal deep-vein thrombosis and/or pulmonary embolism. API-CAT is an international, randomized, parallel-group, double-blind, noninferiority trial with blinded adjudication of outcome events. Consecutive patients are randomized to receive apixaban 2.5 or 5 mg bid for 12 months. The primary efficacy outcome is a composite of recurrent symptomatic or incidental VTE during the treatment period. The principal safety endpoint is clinically relevant bleeding, defined as a composite of major bleeding or nonmajor clinically relevant bleeding. Assuming a 12-month incidence of the primary outcome of 4% with apixaban and an upper limit of the two-sided 95% confidence interval of the hazard ratio <2.0, 1,722 patients will be randomized, assuming an up to 10% loss in total patient-years (ß = 80%; α one-sided = 0.025). This trial has the potential to demonstrate that a regimen of extended treatment for patients with CT beyond an initial 6 months, with a reduced apixaban dose, has an acceptable risk of recurrent VTE recurrence and decreases the risk of bleeding.

Modulating tumor-associated macrophages to enhance the efficacy of immune checkpoint inhibitors: A TAM-pting approach.

Tumor-associated macrophages (TAM) plasticity and diversity are both essential hallmarks of the monocyte-macrophage lineage and the tumor-derived inflammation. TAM exemplify the perfect adaptable cell with dynamic phenotypic modifications that reflect changes in their functional polarization status. Under several tumor microenvironment (TME)-related cues, TAM shift their polarization, hence promoting or halting cancer progression. Immune checkpoint inhibitors (ICI) displayed unprecedented clinical responses in various refractory cancers; but only approximately a third of patients experienced durable responses. It is, therefore, crucial to enhance the response rate of immunotherapy. Several mechanisms of resistance to ICI have been elucidated including TAM role with its essential immunosuppressive functions that reduce both anti-tumor immunity and the subsequent ICI efficacy. In the past few years, thorough research has led to a better understanding of TAM biology and innovative approaches can now be adapted through targeting macrophages' recruitment axis as well as TAM activation and polarization status within the TME. Some of these therapeutic strategies are currently being evaluated in several clinical trials in association with ICI agents. This combination between TAM modulation and ICI allows targeting TAM intrinsic immunosuppressive functions and tumor-promoting factors as well as overcoming ICI resistance. Hence, such strategies, with a better understanding of the mechanisms driving TAM modulation, may have the potential to optimize ICI efficacy.

Management of chordoma of the sacrum and mobile spine.

Chordoma is a very rare, poorly known malignancy, with slow progression, mainly located in the sacrum and spine. All age groups may be affected, with a diagnostic peak in the 5th decade of life. Clinical diagnosis is often late. Histologic diagnosis is necessary, based on percutaneous biopsy. Specific markers enable diagnosis and prediction of response to novel treatments. New radiation therapy techniques can stabilize the tumor for 5 years in inoperable patients, but en-bloc resection is the most effective treatment, and should be decided on after a multidisciplinary oncology team meeting in an expert reference center. The type of resection is determined by fine analysis of invasion. According to the level of resection, the patients should be informed and prepared for the expected vesico-genito-sphincteral neurologic sequelae. In tumors not extending above S3, isolated posterior resection is possible. Above S3, a double approach is needed. Anterior release of the sacrum is performed laparoscopically or by robot; resection uses a posterior approach. Posterior wall reconstruction is performed, with an associated flap. Spinopelvic stabilization is necessary in trans-S1 resection. Total or partial sacrectomy shows high rates of complications: intraoperative blood loss, infection or mechanical issues. Neurologic sequelae depend on the level of root sacrifice. No genital-sphincteral function survives S3 root sacrifice. Patient survival depends on initial resection quality and the center's experience. Immunotherapy is an ongoing line of research.

[Intercontinental Multidisciplinary Oncology Videoconferencing between the South Pacific and the French mainland: Results after one year and 323 cases of rare or complex cancers discussed]. / RCP Pacifique : bilan après un an et 323 cancers rares et/ou complexes discutés.

INTRODUCTION: Overseas France represents 18 % of French territory and is home to 4 % of its population for whom there is unequal treatment in the field of rare/complex cancer. AIM: To report our experience of intercontinental multidisciplinary videoconferencing between the French mainland and Pacific territories. METHODS: Every other friday, three centers located in Papeete, Nouméa and Paris-Villejuif connected between 6:30 AM and 8:00 AM GMT to discuss cases of rare/complex cancers. RESULTS: Between November 2019 and December 2020, 323 presentations implicating 233 patients involved sarcoma (n=93), digestive pathology (n=60), neuroendocrine tumors (n=35), urology (n=24), gynecology (n=24), neurology (n=16), thyroid pathology (n=14), dermatology (n=14), senology (n=11), hematology (n=11), ENT pathology (n=10), pathology thoracic (n=10) and pediatrics (n=1). Of the 233 patients, 134 (57.5 %) living in New Caledonia and 99 (42.5 %) in French Polynesia, 117 (50.5 %) had metastatic disease. 39 patients (16.7 %) were transferred to French mainland (EVASAN), for surgery (n=25), vectorized radiotherapy (n=7), biopsy (n=5), chemotherapy (n=1) or inclusion in a clinical trial (n=1). 195 patients (83.7 %) were treated at home, 15 (6.4 %) are still awaiting a decision and 4 (1.7 %) lost to follow-up. CONCLUSION: The use of videoconferencing to discuss rare/complex cancer cases was effective in guaranteeing French overseas population access to innovative therapies and clinical trials, limiting the need for intercontinental transfer to 16.7 %.

Population Pharmacokinetic Analysis of Pazopanib in Patients and Determination of Target AUC.

Pazopanib is a potent multi-targeted kinase inhibitor approved for the treatment of advanced renal cell carcinoma and soft tissue sarcoma. The pharmacokinetics of pazopanib is characterized by a significant inter- and intra-patient variability and a target through plasma concentration of 20.5 mg·L-1. However, routine monitoring of trough plasma concentrations at fixed hours is difficult in daily practice. Herein, we aimed to characterize the pharmacokinetic (PK) profile of pazopanib and to identify a target area under the curve (AUC) more easily extrapolated from blood samples obtained at various timings after drug intake. A population pharmacokinetic (popPK) model was constructed to analyze pazopanib PK and to estimate the pazopanib clearance of a patient regardless of the time of sampling. Data from the therapeutic drug monitoring (TDM) of patients with cancer at Institute Gustave Roussy and a clinical study (phase I/II) that evaluates the tolerance to pazopanib were used. From the individual clearance, it is then possible to obtain the patient's AUC. A target AUC for maximum efficacy and minimum side effects of 750 mg·h·L-1 was determined. The comparison of the estimated AUC with the target AUC would enable us to determine whether plasma exposure is adequate or whether it would be necessary to propose therapeutic adjustments.