Long-term use of tinzaparin for the treatment of cancer-associated thrombosis in clinical practice: Insights from the prospective TROPIQUE study.

BACKGROUND: Real word data on the efficacy and safety of long-term use of tinzaparin for the treatment of cancer-associated thrombosis (CAT) are scarce. METHODS: We performed a post-hoc analysis of all cancer patients included in the prospective multicenter observational TROPIQUE study who received long-term treatment with tinzaparin for a first venous thromboembolism (VTE) event. We evaluated the patterns of anticoagulant prescription, the adherence to clinical practice guidelines (CPGs) for the treatment of CAT, and the clinical outcomes within a 6-month follow-up. RESULTS: In total, 301 patients were included in this post-hoc analysis. At study entry, their mean age was 64.6±11.9years and 143 (47.5%) patients were men. The most frequent cancer type was gastrointestinal (23.9%), followed by breast (17.9%) and lung (15.3%) cancer. At time of VTE diagnosis, 164 (57.8%) patients had metastatic disease and 245 (81.42%) were receiving chemotherapy. Based on the aggregation of all study pre-defined criteria, tinzaparin prescription was fully compliant with CPGs in 219 (72.8%) patients. The mean effective treatment duration with tinzaparin was 6.07±0.17months. At 6-month follow-up, the cumulative incidence of recurrent VTE was 5.4% (95% CI: 3.2-9.2%) and the cumulative incidence of major bleeding was 5.8% (95% CI: 3.6-9.6%). Clinical outcomes tended to differ across different types of cancer. Death from any cause occurred in 102 (33.9%) patients, mainly related to cancer progression. CONCLUSIONS: This post-hoc analysis of TROPIQUE confirms the favorable benefit-risk ratio of tinzaparin for the long-term treatment of CAT.

Patient education program at the forefront of cancer-associated thrombosis care.

INTRODUCTION: Treatment of cancer-associated thrombosis (CAT) requires specific approaches, although it is well codified in most cases. Current national and international (International Initiative on Cancer and Thrombosis, ITAC) Clinical Practice Guidelines (CPG) recommend the use of low-molecular-weight heparin (LMWH) over 6 months as first treatment option, and anticoagulation should be maintained thereafter as long as cancer is active. Since compliance improves when patients understand their disease and related treatments, we created a dedicated patient education program (PEP) for CAT, aiming to improve quality of care. METHODS: Retrospective analysis of all patients who voluntarily joined the PEP for CAT from 2014 to 2020. RESULTS: In total, 182 cancer patients (median age, 64.9 years) were included, 53.3% with metastatic disease. A total of 528 PEP sessions (median, 3 per patient) were delivered. After PEP completion, the rate of self-injections or those performed at home by a relative had increased from 49.1% to 59.8% (P=0.05). Quality of life had improved significantly (P=0.025) and 90.0% of patients reported adhering to anticoagulant therapy. CONCLUSION: Implementation of a structured and personalized PEP for CAT is feasible, allowing to improve cancer patient empowerment, adherence to CAT treatment and quality of life. The Groupe francophone et cancer (GFTC) members aim at facilitating access to CAT-PEP for both patients and caregivers and use of the multi-language ITAC-CPG mobile app (free access: www.itaccme.com) to improve the care and quality of life of patients with CAT.

[New international guidelines for curative treatment and prophylaxis for venous thromboembolism (VTE) in cancer patients and the dedicated smartphone application]. / Nouvelles recommandations internationales pour le traitement curatif et prophylactique de la maladie thromboembolique veineuse chez les patients atteints d'un cancer et application dédiée pour smartphone.

Venous thromboembolism (VTE) is a frequent and serious complication in cancer patients, and the second leading cause of death in this setting. Cancer patients are also more likely to present recurrent VTE and major bleeding while taking anticoagulants. Management of VTE in these patients is always challenging and remains suboptimal worldwide. In 2013, the International Initiative on Thrombosis and Cancer (ITAC-CME) released international guidelines for the treatment and prophylaxis of VTE and central venous catheter-associated thrombosis, based on a systematic review of the literature ranked according to the Grading of Recommendations Assessment, Development, and Evaluation scale. An update of these ITAC-CME consensus guidelines, including the use of direct oral anticoagulants, was recently published. In this review, we summarize these updated guidelines. Better adherence to the international guidelines, involving an adequate educational and active implementation strategies, will substantially decrease the burden of VTE and allow to increase survival in cancer patients.

Effect on survival of local ablative treatment of metastases from sarcomas: a study of the French sarcoma group.

AIMS: Recent data suggest that patients with pulmonary metastases from sarcomas might benefit from ablation of their metastases. Some data are available regarding osteosarcomas/angiosarcomas and lung metastases. The purpose of this study was to assess the efficacy of local ablative treatment on the survival of patients with oligometastases (one to five lesions, any metastatic site, any grade/histology) from sarcomas. MATERIALS AND METHODS: A multicentric retrospective study of the French Sarcoma Group was conducted in sarcoma patients with oligometastases who were treated between 2000 and 2012. Survival was analysed using multivariate sensitivity analyses with propensity scores to limit bias. RESULTS: Of the 281 patients evaluated, 164 patients received local treatment for oligometastases between 2000 and 2012. The groups' characteristics were similar in terms of tumour size and remission of the primary tumours. The median follow-up was 25.7 months; 129 (45.9%) patients had died at this point. The median overall survivals were 45.3 (95% confidence interval = 34-73) months for the local treatment group and 12.6 for the other group (95% confidence interval = 9.33-22.9). Survival was better among patients who received local treatment (hazard ratio = 0.47; 95% confidence interval = 0.29-0.78; P < 0.001). Subgroup analyses revealed similar findings in the patients with single oligometastases (hazard ratio = 0.48; 95% confidence interval = 0.28-0.82; P = 0.007); a significant benefit was observed for grade 3, and a trend was observed for grade 2. CONCLUSION: Local ablative treatment seemed to improve the overall survival of the patients who presented with oligometastatic sarcomas, including soft tissue and bone sarcomas. The survival benefit remained after repeated local treatments for several oligometastatic events. Surgery yielded the most relevant results, but alternative approaches (i.e. radiofrequency ablation and radiotherapy) seemed to be promising. The relevance of these results is strengthened by our analysis, which avoided biases by restricting the population to patients with oligometastatic disease and used propensity scores.

[Impact of omission of axillary dissection on adjuvant therapy in patients with metastatic sentinel lymph nodes according to the ACOSOG Z0011 criteria]. / Impact de l'omission du curage axillaire sur les traitements adjuvants chez les patientes ayant un ganglion sentinelle métastatique et répondant aux critères d'inclusion de l'ACOSOG Z0011.

OBJECTIVES: The results of the ACOSOG Z0011 questioned the usefulness of axillary lymph node dissection (ALND) in case of metastatic sentinel lymph node (SLN). The aim of our study was to assess the impact of the omission of ALND according to the inclusion criteria of the ACOSOG Z0011 study if SLN are metastatic but also the consequences on prescription of the application of a new standard of care for adjuvant treatment. PATIENTS AND METHODS: This retrospective study included, between November 2007 and January 2012, patients with T1-T2N0 breast cancer and metastatic SLN meeting the criteria for omission of completion ALND according to the study of the ACOSOG Z0011. Patients were submitted anonymously and randomly in multidisciplinary meeting (MM) 3 times: with complete information including ALND (MM1), with information from SLN alone (MM2) and with complete information of ALND according to the current protocols in 2013 (MM3). During each presentation, we collected the decision of the different adjuvant treatments proposed: chemotherapy, hormonal therapy, radiotherapy (with radiation fields). Then, we compared therapeutic proposals of the 3 presentations. RESULTS: Fifty-eight patients were eligible for inclusion criteria of the ACOSOG Z0011. Treatments actually proposed during MM1 consisted of 94.8 % of chemotherapy, 77.6 % of breast and lymph nodes radiotherapy and 91.4 % of hormone therapy. During the MM2, there was no significant difference compared to the decision taken during MM1. In fact, during MM2, we decided chemotherapy, radiotherapy and hormonotherapy respectively in 89.7, 79.3 and 91.4 % of the cases. During the MM3, it was shown a significant decrease in the indications of chemotherapy (82.8 %, P=0.03) and lymph nodes irradiation (56.9 %, P=0.02) compared to the therapeutic proposals of the MM1. DISCUSSION AND CONCLUSION: The lack of information of ALND does not seem to significantly alter indications for adjuvant treatment. Otherwise, the evolution of our references causes a decrease in adjuvant therapy.

Optimization of cisplatin doses in a testicular cancer patient with acute renal failure.

Although testicular cancers are highly curable malignancies, conventional cisplatin based therapy often causes important toxicities, not often easily manageable. Nephrotoxicity occurs in almost all patients, and is potentialized in patients suffering from renal failure. Monitoring of residual levels of unbound platinum was used to define guidelines for cisplatin administration. Monitoring of cisplatin was initiated in a patient treated for metastatic testicular cancer and acute renal failure. Reduced doses of cisplatin were first administered in conjunction with hemodialysis. Unbound and total platinum levels were determined by flameless atomic absorption spectrophotometry. The data found allowed us to adapt and increase sequentially cisplatin doses, accordingly with the renal function. Full regimen doses were eventually administered when useful renal function returned. This simple approach may be useful in monitoring cisplatin administration during acute renal failure.

[Abdominal pain during the course of lung cancer]. / Douleur abdominale au cours de l'évolution d'un cancer bronchique.

INTRODUCTION: Metastatic involvement of the peritoneum from a lung cancer is infrequently encountered. METHODS: We present the case report of a patient with bronchial adenocarcinoma whose course is complicated by the occurrence of a peritoneal carcinomatosis, as documented by FDG-PET. CONCLUSION: Unexplained abdominal pain in a lung cancer patient may be a peritoneal carcinomatosis. The diagnosis can be helped by PET-scan. However, the therapeutic opportunities are very limited.

[The consequences of passive smoking in adults]. / Conséquences du tabagisme passif chez l'adulte.

INTRODUCTION: Passive smoking is the involuntary inhalation by a non-smoker of smoke generated in his neighbourhood by one or more smokers. BACKGROUND: The effect of this exposure is already generally recognised in children. In adults the induction of chronic obstructive lung disease has not been demonstrated. This is no longer the case for ischaemic heart disease and lung cancer where the effect of passive exposure of non-smokers to cigarette smoke is recognised. The biological plausibility together with the concordance of results obtained over successive years, as well as the large numbers of patients included in the studies, lead to a confident conclusion that the risks in adult non-smokers are increased by the order of 25%. CONCLUSIONS: There is no evidence that bias affects the conclusions reached and the World Health Organisation has recently classified passive smoking as being carcinogenic in man. As a result of these data prevention of passive exposure to cigarette smoke should be part of a larger framework of smoking prevention, especially among the young.

Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol.

BACKGROUND: We conducted a phase II study to evaluate in 72 adult patients the efficacy of the intensive LMB chemotherapy regimen, previously reported by the Société Française d'Oncologie Pédiatrique for children with Burkitt lymphoma and L3 acute lymphoblastic leukemia. PATIENTS AND METHODS: Treatment began with a prephase (low-dose steroids, vincristine and cyclophosphamide), except in patients with low tumor burden. Group A (resected stage I and abdominal stage II disease) received three courses of vincristine, cyclophosphamide, doxorubicin and prednisone. Group B (not eligible for groups A or C) received five courses of chemotherapy comprising high-dose methotrexate, infusional cytarabine and intrathecal (IT) methotrexate. Group C (patients with central nervous system and/or bone marrow involvement with < 30% of blast cells) received eight courses containing intensified high-dose methotrexate, high-dose cytarabine, etoposide and triple IT injections. RESULTS: The 2 year event-free survival and overall survival rates for the 72 patients were 65% and 70%, respectively. Age > or = 33 years and high lactate dehydrogenase value were associated with a shorter survival. No response to COP was also associated with a poor outcome in group B. CONCLUSION: Patients with advanced-stage Burkitt lymphoma, including those with bone marrow and/or central nervous system involvement, can be cured with a short-term intensive chemotherapy regime tailored to the tumor burden.

Continuous infusion of vincristine-doxorubicin with bolus of dexamethasone(VAD) alternated with CHEP in the treatment of patients over 60 years old with aggressive non-Hodgkin's lymphoma.

This prospective study was undertaken to evaluate the efficacy and toxicity of combination chemotherapy with alternating cycles of vincristine, doxorubicin and dexamethasone (VAD) and cyclophophamide, doxorubicin, etoposide and prednisone (CHEP) in patients over 60 years old with previously untreated and advanced non-Hodgkin's lymphoma (NHL) of intermediate- and high-grade malignancy. Eighty one consecutive, patients with NHL referred from April 1992 to October 1997 to GOELAMS centers were enrolled in this study and their outcome updated to June 1, 1999. Of 81 enrolled patients, 77 were eligible and assessable for response. The median age was 70 years (61 to 78), 85.7% were stage III or IV, 39% were of performance status > or = 2, 27.3% > or = 2 involved extra-nodal sites and 57.3% had higher LDH levels than normal. The immunophenotype was B in 87% and T in 13%. Fifty-one (66.2%) patients received the scheduled eight cycles of therapy and treatment was withdrawn in only 6 patients (7.8%) because of toxicity. Neutropenia grade 3-4 occurred in 11.1% after VAD courses vs 40.6% after CHEP courses. The mean cumulative dose of doxorubicin was 269 mg/m2 and the relative dose intensity was 84%. The overall response and complete response rates were 66.2% and 51.9% respectively, and after a median follow-up of 52 months the 3 year overall survival (OS) and event-free survival rates (EFS) were 43.5% and 33.0% respectively. In multivariate analysis, OS and EFS were statistically influenced by IPI (p = 3 x 10(-3); p < 1 x 10(-4)) and phenotype (p = 2 x 10(-3); p < 1 x 10(-4)). Our findings support the alternation of 4 courses of VAD and CHEP as it is well tolerated in patients over 60 years old with advanced intermediate- or high-grade NHL and provides response and survival rates comparable to 6 courses of CHOP.

Infradiaphragmatic Hodgkin's disease: long term results of combined modality therapy.

Hodgkin's disease (HD) confined below the diaphragm accounts for less than 5% of all patients with HD. Although the major characteristics of this presentation appear established, optimal modalities of treatment still remain difficult to define. From April 1972 to October 1988, 28 patients with newly diagnosed infra-diaphragmatic HD, clinical stages I or II have been treated with 3 successive prospective protocols combining initial chemotherapy and radiotherapy (40 gy). This series of patients accounted for 4,3% of patients with HD limited to clinical stages (CS) I and II. Overall survival and freedom from relapse at 15 years were 74,4% and 73% respectively, without significant differences between clinical stages I and II, presence or absence of B symptoms or histologic subtype. There is only a trend (p < 0,10) in favour of patients younger than 40 years. In all 7 clinically staged IA patients no relapses were seen and combined treatment does not appear to be better than inverted Y irradiation alone. On the other hand initial chemotherapy seems necessary in patients with CS II A and B since 15 of our 21 patients are alive in first CR whereas the crude rate of transdiaphragmatic nodal relapses may reach up to 53% following radiotherapy alone.

Hodgkin's disease during HIV1 infection: the French registry experience. French Registry of HIV-associated Tumors.

BACKGROUND: The first cases of Hodgkin's disease (HD) associated with HIV infection were reported in 1984. Since then, short series of seropositive patients suffering from HD have been published. In order to identify the characteristics, treatment response and outcome of HIV-associated Hodgkin's disease (HIV-HD), the data of HIV-HD patients recorded between 1987 and 1989 were analysed and compared with those of primary HD patient and with those of HIV-associated non-Hodgkin's lymphoma (HIV-NHL), registered during the same period. PATIENTS AND METHODS: The 45 cases of HD collected by the French registry of HIV-associated tumors between January 1987 and December 1989 were included in this study. All patients were clinically staged according to the Ann Arbor system. To compare HIV-HD characteristics with those of primary HD, we used a cohort of 407 patients with clinical stages (CS) IA to IVB, who were enrolled between September 1981 and August 1988 in a multicentric clinical trial. To identify the relationship between HIV-HD and the course of HIV infection we studied, when available, the routes of infection, initial CD4 cell count at the moment of HD diagnostic as well as the CDC class of HIV infection and compared these data with the same parameters observed in 142 HIV-NHL enrolled in the registry during the same period. RESULTS: HIV-HD is characterized by an increase in mixed-cellularity histology (49%), with a predominance of advanced stages (75%) and B symptoms (80%). A unique observation is made regarding mediastinal involvement, present in only 13% of HIV-HD (71% in primary HD). The HIV-HD/HIV-NHL ratio was significantly higher in intravenous drug abusers than in male homosexuals. Median CD4 cell count was 306/microliters at HIV-HD diagnosis, and only 11% of the cases were preceded by an AIDS manifestation. With standard therapy, 79% of the patients achieved complete remission, but hematological and infectious complications were very frequent. The progression to AIDS rate was 94% at two years and opportunistic infections were the most frequent cause of death. Overall two-year survival was 41% with 71% for patients with initial CD 4 cell counts higher than 300/microliter and 0% for those with CD4 cell counts lower than 300/microliter (P < 0.01). CONCLUSION: HIV-HD has a particular clinico-pathological profile when compared to primary HD, with a predominance of mixed-cellularity type, a high frequency of advanced stages and a high proportion of patients without mediastinal involvement. Moreover, HIV-HD seems to occur preferentially in the group of subjects infected by needle sharing. Standard HD therapy seems to be efficient but excessively toxic.

Combined differentiation therapy in myelodysplastic syndrome with retinoid acid, 1 alpha,25 dihydroxyvitamin D3, and prednisone.

The myelodysplastic syndrome (MDPS) provides an opportunity for identifying host factors (genetic, endocrine, immune) involved in initiation and progression of preleukemia into frank acute myeloid leukemia. The aim of this study was to identify bone marrow (BM) cellular and humoral dysfunctions central to the development of MDPS and useful in therapeutic follow-up studies. Our preclinical studies have shown that (1) the characteristic stromal cell composition of the normal BM microenvironment was impaired in MDPS and in AML in 67 and 86% of the cases, respectively; (2) the 1 alpha,25(OH)2D3 concentration in BM plasma was abnormal in 50% of MDPS and 30% of AML; and (3) an inverse correlation existed in MDPS between the 1 alpha,25(OH)2D3 concentration and the frequency of F-CFU, (r = 0.41, p < 0.02), suggestive of a regulatory interaction between this secosteroid hormone and BM stromal cells. The analysis of clonal extinction of BM blast cells in response to all trans retinoic acid (RA), 1 alpha,25(OH)2D3, and colony stimulating factors (PHA-LCM), either alone or in various combinations, revealed individual patterns of responses in the cases of MDPS or AML. The results indicate the necessity for preclinical studies to select patients for combined differentiation therapy. Our ongoing clinical trials suggest that RA (Roaccutan, 20 mg/day continuously) as induction therapy, followed at weeks 6 to 8 by prednisone (40 mg/day for 15 days) and 1 alpha,25(OH)2D3 (Rocaltrol, 3 x 0.25 micrograms/day for 3 months) may induce a long-lasting hematological remission in MDPS.