Lee 350 1Low molecular weight heparins are generally considered to be the preferred first-line treatment for acute venous thromboembolism in patients with active cancer. However, this recommendation is mainly based on results of the phase III CLOT study, dating back to the late nineties. Given the lack of confirmatory trials or trials including different medications, warfarin remains a commonly used anticoagulant treatment in cancer patients. In order to confirm previous findings that LMWHs are superior to warfarin in preventing recurrent VTE among cancer patients, a total of 900 cancer patients with DVT or PE were enrolled in an international, randomized, phase III trial comparing the efficacy and safety of the LMWH tinzaparin with warfarin. The results of this phase III CATCH study were recently published in the journal of the American Medical Society (JAMA). This study revealed that, in patients with active cancer and acute VTE, tinzaparin reduced the risk of recurrent VTE from 10% to 6.9%, significantly lowered the risk of symptomatic DVT by 52% (p=0.04) and did not increase major bleeding despite full dose. Moreover tinzaparin significantly reduced the incidence of clinically relevant non‐major bleeding (p=0.03). As the largest randomized, controlled trial on the treatment of thrombosis among cancer patients, CATCH provides a more contemporary and global evidence for long-term LMWH therapy.

The 900 patients In CATCH were randomized to receive either tinzaparin (175 IU/kg once daily for 6 months; N= 449) or initial tinzaparin (175 IU/kg once daily for 5–10 days) overlapped and followed by dose-adjusted warfarin (target INR 2.0–3.0) (N= 451) for 6 months. The primary efficacy outcome was time to recurrent VTE verified by objective, standard imaging and blinded central adjudication; this was a composite primary endpoint that included symptomatic DVT and/or PE, incidental proximal DVT and/or PE and fatal PE. The primary safety endpoint was incidence of major bleeding, while clinically relevant non-major bleeding and overall mortality were also assessed.

During the treatment period, 31 patients (7.2%) treated with tinzaparin experienced recurrent VTE compared with 45 (10.5%) in the warfarin arm. This translates into a 35% reduction in the risk for a recurrent VTE (HR[95%CI]: 0.65[0.41–1.03]; p= 0.07). Symptomatic non-fatal DVT occurred in 12 patients (2.7%) in the tinzaparin arm and 24 (5.3%) in the warfarin arm (HR[95%CI]: 0.48[0.24–0.96]; p= 0.04). Symptomatic non-fatal PE occurred in 3 tinzaparin patients and in 2 treated with warfarin. Fatal PE, on the other hand, occurred in 17 (3.8%) patients in each arm (HR[95%CI]: 0.96[0.49–1.88]; p= 0.90). There was no difference in the incidence of major bleeding events (2.9% in the tinzaparin arm and 2.7% in the warfarin arm, HR[95%CI]: 0.89[0.40-1.99]; p=0.77). However, significantly fewer patients experienced clinically relevant non-major bleeding with tinzaparin as compared to warfarin (10.9% vs. 15.3% respectively; HR[95%CI]: 0.58[0.40-0.84]; p= 0.004) (Figure 1).

In summary, CATCH is an important study as it confirms the preferred role of LMWHs in the initial and long-term treatment of CAT. CLOT previously demonstrated the superior efficacy and safety of LMWHs over warfarin in the prevention of recurrent VTE in cancer patients. The CATCH study now validates and confirms these findings in a much larger trial. As such, these findings are reassuring as they confirm the current international treatment recommendations.

Figure 1. CATCH safety outcome analysis.

abstract1 figure1a

 

Reference

Lee A, Kamphuisen P, Meyer G et al. Tinzaparin vs Warfarin for Treatment of Acute Venous Thromboembolism in Patients With Active Cancer: A Randomized Clinical Trial. JAMA 2015;324(7):677-86.


Carrier 350The prevalence of occult cancer is low in patients with a first unprovoked venous thromboembolism, according to results from a multicenter, randomized study presented at the 2015 ISTH Congress. The results of this study were recently also published in the New England Journal of Medicine. In addition, routine screening with the addition of a comprehensive computed tomography (CT) scan of the abdomen and pelvis was no better than routine screening alone in detecting occult cancer in this population.

The Screening for Occult Malignancy in Patients with Idiopathic Venous Thromboembolism (SOME) trial was a multicenter, open-label, randomized, controlled trial that compared the efficacy of conventional screening with comprehensive CT of the abdomen/pelvis for detecting occult cancers in patients with unprovoked venous thromboembolism (VTE).

It has been described that up to 10% of patients with unprovoked VTE are diagnosed with cancer in the year following their VTE diagnosis. Therefore, it is appealing for clinicians to screen these patients for occult cancer but it has led to a lot of diversity in practices. Some clinicians prefer to use a limited screening strategy that would include a history, physical examination, routine blood tests and a chest X-ray. Other clinicians prefer to use the limited screening strategy in combination with additional tests. That could be CT of the abdomen and pelvis, ultrasound, or tumor marker, or CAT scan. It’s hard for a physician to know what to use.

For the SOME trial, a total of 854 patients with unprovoked VTE were randomized to two groups: 431 to limited occult cancer screening (basic blood work, chest X-ray and breast/cervical/prostate cancer screening), and 423 to limited screening in combination with a comprehensive CT of the abdomen/pelvis. The comprehensive CT included a virtual colonoscopy and gastroscopy, a biphasic enhanced CT, a parenchymal pancreatogram and a uniphasic enhanced CT of distended bladder. The primary outcome was confirmed cancer that was missed by the screening strategy and detected by the end of the one-year follow-up period.

In total, 33 patients (3.9%) had a new diagnosis of cancer in the interval between randomization and one-year follow-up: 14 in the limited screening group and 19 in the limited screening plus CT group, a difference that was not statistically significant (p= 0.28). In addition, the number of occult cancers missed by the end of the one-year follow-up period was similar between the two groups: 4 in the limited screening group and 5 in the limited screening plus CT group (Figure 1). Carrier et al. also found no significant differences between the limited screening group and the limited screening plus CT group in the rate of detection of early cancers (0.23% vs. 0.71%, respectively; p= 0.37); in overall mortality (1.4% vs. 1.2%; p > 0.99), or in cancer-related mortality (1.4% vs. 0.95%; p= 0.75).

The prevalence of occult cancer was low among patients with a first unprovoked venous thromboembolism. Routine screening with CT of the abdomen and pelvis did not provide a clinically significant benefit. These results suggest that a limited screening strategy for occult cancer (history taking, physical examination, basic blood testing, chest radiography, and age-specific and sex-specific cancer screening) may be adequate for patients who have a first unprovoked venous thromboembolism.

Figure 1. time to detection of a missed occult cancer over the 1-year follow-up period indicated no significant between-group difference.

abstract2 figure1

 

Reference

Carrier M, Lazo-Langner A, Shivakumar S et al. Screening for Occult Cancer in Unprovoked Venous Thromboembolism. N Engl J Med 2015;373(8):697-704.


Noble 350Thrombosis remains the most common preventable cause of mortality in cancer patients receiving chemotherapy. Whilst the prophylaxis and treatment of this condition is well understood, the patient experience and subsequent behavioral factors are not. To gain more insight in this, Noble et al conducted a qualitative study to explore the wider patient experience of living with cancer-associated thrombosis (CAT). The main objectives of this study were to explore how the CAT journey impacted the patient experience, the impact of the treatment for CAT on the patients, the emotional impact of CAT and the unmet areas of need within the CAT journey.

Patients receiving treatment for CAT were interviewed about their experiences of CAT within the context of their cancer journey. Twenty interviews were transcribed and analyzed using framework analysis.

Chemotherapy patients were well informed about the risks of febrile neutropenia, how to recognize it, and when to seek medical attention. However, they had limited knowledge about CAT and received no information about the condition. Red flag symptoms suggestive of CAT were attributed to chemotherapy or the underlying cancer, resulting in delayed presentation to hospital, and diagnosis. The CAT journey was considered a distressing one, with limited support or information, in complete juxtaposition with the treatment they received for their cancer. Patients felt there was little ownership for the management of CAT, which further added to their distress.

In summary, CAT is a common occurrence and patients view their experiences of it within the context of their overall cancer journey. However, patients receive little information to help recognize CAT and access timely treatment on the development of symptoms. Whilst other cancer complications have clear treatment pathways, thrombosis does not appear to have been afforded the same priority. A proactive approach to increase patient awareness, coupled with established CAT pathways is likely to reduce mortality, morbidity, and long-term psychological distress.

 

Reference

Noble S, Prout H, Nelson A. Patients’ Experiences of LIving with CANcer-associated thrombosis: the PELICAN study. Patient Prefer Adherence 2015;9:337-45.


WTD 350Recognized on 13 October, World Thrombosis Day (WTD) focuses attention on the often overlooked and misunderstood disease of thrombosis. With hundreds of educational events in countries around the world, WTD and its partners place a global spotlight on thrombosis as an urgent and growing health problem. World Thrombosis Day takes place every year on 13 October, the birthday of Rudolf Virchow who was a pioneer in the pathophysiology of thrombosis. A German physician and pathologist, Virchow developed the concept of "thrombosis" and advanced our understanding of this condition.

The main objectives of this initiative are to:

  • Highlight the burden of disease (thrombosis in general) and highlight the need for action, specifically underscoring the unrecognized threat and serious consequences (morbidity and mortality) related to venous thromboembolism (VTE).
  • Increase public awareness of the significance, risks, signs and symptoms of VTE.
  • Empower individuals to seek medical attention promptly if they have signs or symptoms, and to engage their healthcare providers in discussions about appropriate diagnosis, prevention and treatment options.
  • Galvanize organizations in countries across the globe to conduct appropriate and aligned campaigns in their countries and regions.
  • Begin the process of advocating for "systems of care" to properly prevent, diagnose and treat VTE

For more information on world thrombosis day and a complete overview of initiatives please visit www.worldthrombosisday.org


Clot spotWhile pulmonary embolisms may be fatal, many people live through them. Unfortunately there is little information available on pulmonary embolism recovery. The Clot Spot provides information about pulmonary embolisms, common blood clotting conditions (thrombophilia), common recovery experiences, and treatment options.

The Clot Spot (www.clotspot.com) seeks to fill in the missing information regarding recovery and assist survivors throughout the pulmonary embolism recovery journey. The Clot Spot is not a replacement for a strong medical team, as such it is important to take information that patients find on this site to the consultation room and share it with their doctor. Nevertheless, self-education is a wonderful tool in recovery and can open up empowering conversations with your treating physicians. Living life as a survivor is an educational journey even after the pulmonary embolism has healed.

In addition to information on the prevention and treatment of pulmonary embolism, the clot spot website also includes a forum that allows patients to share their experiences.


Verhamme 350Professor Peter Verhamme summarizes the key messages of the phase III CATCH trial:

  1. CATCH confirms the superior efficacy of low-molecular-weight heparins over vitamin K antagonists in the treatment of cancer associated thrombosis
  2. Tinzaparin was associated with less clinically relevant bleedings in patients with cancer associated thrombosis
  3. CATCH confirms the validity of the current international treatment guidelines in the management of cancer associated thrombosis