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Delphi Consensus on the Follow-up of Cancer Patients with Breakthrough Pain Under Opioid Treatment

  • José Luis Larriba GonzálezEmail author
  • Diego Cayuela López
  • Ovidio Fernández Calvo
  • Salvador Garcerá Juan
  • Raquel Molina Villaverde
  • Juan José Reina Zoilo
  • Vicente Guillém
  • Carlos Camps
  • Margarita Feyjóo
Medicine
  • 64 Downloads
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  1. Topical Collection on Medicine

Abstract

Background

Breakthrough cancer pain (BTcP) is one of the most common symptoms related to the disease and its treatment. Its management differs from that of chronic pain but there is not a wide consensus about fundamental aspects of BTcP definition, diagnosis, follow-up, and management. The objective of this study is to reach a consensus on the follow-up of patients with BTcP under opioid treatment.

Background

This work was conducted using a modified Delphi method organized in two rounds and involving a panel of 84 medical oncologists. A questionnaire of 66 items was developed with the following topics: (1) When to perform the first and subsequent BTcP treatment evaluations; (2) What to assess at the first follow-up visit and how; and (3) What to assess in the following visits and how.

Results

After two rounds, a consensus was reached in 53 of 66 items proposed (80.3%). The main agreements reached include: The first follow-up visit should preferably be face-to-face; increase the number of visits after detecting poor control of BTcP; assess pain control episodes of BTcP in the first and following visits; adjust treatment dose of opioids due to poor control of BTcP; and adopt measures to prevent aberrant opioid-induced behaviors when treating BTcP in patients with cancer.

Conclusion

This Delphi consensus highlights the different points of view of medical oncologists regarding the follow-up of patients with BTcP under opioids treatment. Nonetheless, the conclusions reached can facilitate optimizing monitoring of these patients and promote long-term effectiveness of BTcP control.

Keywords

Cancer Pain Follow-up Analgesic Opioid 

Introduction

Cancer patients must deal with pain, one of the most common symptoms related to the disease and its treatment. The prevalence of pain in these patients ranges from 39.3% after curative treatment, 55.0% during anticancer treatment, and 66.4% in advanced, metastatic, or terminal disease [1]. Cancer pain can be classified in terms of its intensity (mild, moderate, or intense), duration (acute or chronic), and physiopathology (nociceptive, neuropathic, or mixed) [2]. Patients with cancer-related chronic pain usually experience fluctuations in pain intensity that occur as discrete transient pain flares. When these flares interrupt a tolerable background pain, they are commonly described as breakthrough pain [3].

Although there is no commonly agreed definition of breakthrough cancer pain (BTcP), the most widely accepted is “a transient exacerbation of pain that occurs either spontaneously, or in relation to a specific predictable or unpredictable trigger, despite relatively stable and adequately controlled background pain” [4]. Patients suffering from BTcP have decreased functional capacity and increased risk of depression and anxiety. This pain has an important social cost, since it affects productivity, and also has a great impact on the quality of life of patients and their caregivers [5]. The diagnostic algorithm for BTcP proposed by Davies is widely used in clinical practice [4, 6], and there are also two assessment tools to discriminate BTcP from uncontrolled background pain, such as the breakthrough pain assessment tool (BAT) and the Alberta Breakthrough Pain Assessment Tool (ABPAT) [7, 8]. The objective of the treatment of BTcP is to minimize the intensity and severity of each pain episode, and to reduce its impact on patients’ quality of life.

Opioids represent the cornerstone of treatment for acute and chronic pain, including BTcP [9]. However, the characteristics of BTcP make its management different from chronic pain. The slow onset of action of opioids (20–30 min, reaching a peak of analgesia in 60–90 min) results in delayed or ineffective analgesia, while the prolonged duration of effect (3–6 h) results in ongoing adverse events [10]. A meta-analysis concluded that the efficacy of rapid-onset opioids (such as fentanyl) is superior to oral morphine in control of BTcP [11]. The European Society for Medical Oncology (ESMO) and the Spanish Society of Clinical Oncology (SEOM) recommend the use of transmucosal fentanyl to treat BTcP [2, 6].

Because pain may change as the disease and treatment progress, it is necessary to follow the patient from the beginning, not only at the time of drug titration [12]. In addition, despite the efficacy of opioids in cancer patients, recent publications have stated that there are concerns about their inappropriate use, with aberrant opioid-induced behaviors from about 8–19% in patients taking rapid-onset opioids or traditional short-acting oral opioid for BTcP [13, 14]. Some measures adopted in order to prevent this misuse include increase awareness for early detection of risk factors (addictive personality or psychiatric illness), select the appropriate rescue drug for BTcP when risk factors are detected, recruit relatives to oversee patient at home, avoid prescribing rapid-onset opioids off-license, and monitor patients regularly [14].

The aim of this study is to gather the opinion of a panel of Spanish experts about the follow-up of patients in whom treatment for BTcP has been prescribed, and to reach a consensus using a modified Delphi method.

Methods

Study Design

This study was performed according to a modified Delphi method with the aim of reaching a consensus on the follow-up of patients with BTcP under opioid treatment. The process was developed in 4 stages: (1) constitution of the scientific committee in charge of the project; (2) a face-to-face start-up meeting to raise the main topics; (3) two successive rounds of online surveys to gather the opinion of a panel of experts; and (4) result analysis and conclusions discussion by the scientific committee in a face-to-face meeting. The study was approved by the Clinical Research Ethics Committee of the Hospital Clínico San Carlos (Madrid, Spain).

Participants

Three groups were involved in the study: scientific committee, assistance team, and expert panel. The scientific committee coordinated the entire consensus and developed the questionnaire, and was made up of six medical oncologists with more than 3 years of clinical experience in the treatment of patients with cancer and BTcP. The Research Unit of Luzan 5 was the assistance team, which was responsible for the distribution and analysis of the questionnaires. The expert panel was selected by the scientific committee and included 84 medical oncologists with experience in cancer pain. They were responsible for answering the questionnaire.

Questionnaire

In the face-to-face start-up meeting, the scientific committee discussed the main monitoring strategies during the period of maintenance of patients receiving treatment for BTcP according to the clinical experience of each expert, taking into account the individual characteristics of patients (fragility, age, comorbidities, treatment received, drug interactions, etc.). As a result of this meeting, it was agreed a questionnaire of 66 items in Spanish grouped in the following topics: (1) When to perform the first and subsequent BTcP treatment evaluations (11 items); (2) What to assess at the first follow-up visit and how (17 items); and (3) What to assess in the following visits and how (38 items).

A unique 9-point ordinal Likert-type scale was proposed to answer the items (minimum 1, full disagreement; and maximum 9, full agreement) [15]. This scale was structured in three groups according to the level of agreement-disagreement of the item: from 1 to 3, interpreted as disagreement; from 4 to 6, interpreted as neither agreement nor disagreement; and from 7 to 9, interpreted as agreement.

The Delphi Rounds and Consensus Meeting

The Delphi study was conducted over two rounds held between May and June 2018. In the 1st round, expert panelists answered the questionnaire via online offering the possibility of adding their opinion in open text. In the 2nd round, panelists contrasted their personal opinion with that of the other participants and, if necessary, reconsidered their initial opinion on those items where consensus was not reached at 1st round. The results of round 2 were tabulated and presented descriptively. The project was closed on September 2018 with a face-to-face meeting of the scientific committee to debate and interpret the results.

Analysis and Interpretation of Results from the Questionnaires

The final opinion on each of the items was studied through the score and the level of consensus reached by panelists. The same criteria were followed for each of the items. No consensus was reached when the scores of a third or more of panelists were in the 1–3 range, and another third or more in the 7–9 range. On the other hand, there was consensus when less than a third of the responders scored outside the 3-point range (1–3, 4–6, or 7–9) containing the median. The type of consensus achieved on each item was determined by the median value of the score. There was an agreement if the median was ≥ 7, and there was disagreement if the median was ≤ 3. When the median score was located between a 4–6 range, the items were uncertain for a representative majority of the group. A clearer consensus was reached when the score of an item was closer to 1 or 9, either in disagreement or agreement, respectively.

Results

Of the 84 experts consulted, 82 completed the two rounds of the Delphi consensus without proposing new items. In round 1, consensus was reached in 42 of 66 items; all in agreement. Twenty-four items were returned for reconsideration in round 2 and consensus was reached in 11 items; 9 in agreement and 2 in disagreement. After two rounds, a consensus was reached in 53 items (80.3%); 51 in agreement (77.3%) and 2 in disagreement (3.0%). The remaining 13 items (19.7%) did not show agreement or disagreement. Figure 1 depicts the results of the two rounds and Tables 1 and 2 show the global results for all items analyzed.
Fig. 1

Main results of the Delphi consensus

Table 1

Agreement achieved by the experts after the two rounds (topics 1 and 2)

 

Median

(IQR)

Agreement

(%)

Topic 1: When to perform the first and subsequent BTcP treatment evaluations

  1. The first follow-up visit should be done at 48–72 h after start BTcP treatment.

8 (2)

88.24

  2. The first follow-up visit is recommended to be face-to-face.

8 (2)

77.65

  3. The first follow-up visit can be by telephone

7 (2)

56.46

  4. Telephone follow-up of patients with BTcP, when resources are available, is an effective strategy for evolutionary control.

8 (1)

85.88

  5. The following visits should coincide with regular medical visits.

7 (2)

70.59

  6. The following visits should be done whenever required by the patient.

7 (2)

74.12

  7. More frequent visits are needed in patients with impaired liver function.

7 (2)

56.47

  8. More frequent visits are needed in patients with impaired renal function.

7 (1)

68.23

  9. More frequent visits should be done after detecting poor control of BTcP.

8 (2)

98.82

  10. More frequent visits should be done whenever basal pain management (not BTcP management) is changed.

7 (1)

67.06

  11. More frequent visits should be done whenever BTcP treatment is modified.

7 (2)

67.06

Topic 2: What to assess at the first follow-up visit and how

  12. In the first follow-up visit, the number of BTcP episodes per day must be evaluated.

9 (1)

98.82

  13. In the first follow-up visit, the characteristics of BTcP must be assessed (duration, intensity, irradiation, interference with activities of daily living, factors that alleviate or aggravate it).

9 (1)

94.12

  14. In the first follow-up visit, it is necessary to assess the control of BTcP episodes.

9 (1)

97.65

  15. In the first follow-up visit, it is necessary to assess the need to adjust doses due to poor control of BTcP.

9 (1)

98.83

  16. In the first follow-up visit, adherence to treatment for BTcP should be assessed.

9 (1)

96.47

  17. In the first follow-up visit, it is necessary to assess how the patient registers the episodes of BTcP.

8 (2)

92.94

  18. In the first follow-up visit, patient should be recommended to record the number of BTcP episodes per day.

8 (1)

91.76

  19. One of the adverse events to consider at the first follow-up visit of patients under treatment for BTcP is constipation.

8 (2)

85.89

  20. One of the adverse events to consider at the first follow-up visit of patients under treatment for BTcP is nausea.

8 (1)

90.59

  21. One of the adverse events to consider at the first follow-up visit of patients under treatment for BTcP is mental confusion.

8 (2)

83.53

  22. One of the adverse events to consider at the first follow-up visit of patients under treatment for BTcP is pruritus.

5 (2)

17.65

  23. One of the adverse events to consider at the first follow-up visit of patients under treatment for BTcP is dyspnea.

4 (4)

21.18

  24. One of the adverse events to consider at the first follow-up visit of patients under treatment for BTcP is immunosuppression.

3 (2)

0.0

  25. One of the adverse events to consider at the first follow-up visit of patients under treatment for BTcP is urinary retention.

6 (1)

48.24

  26. One of the adverse events to consider at the first follow-up visit of patients under treatment for BTcP is dizziness.

8 (2)

83.52

  27. One of the adverse events to consider at the first follow-up visit of patients under treatment for BTcP is delirium.

7 (3)

71.76

  28. One of the adverse events to consider at the first follow-up visit of patients under treatment for BTcP is diaphoresis.

7 (2)

54.12

BTcP, breakthrough cancer pain; IQR, interquartile range

Table 2

Agreement achieved by the experts after the two rounds (topic 3)

Topic 3: What to assess in the following visits and how

Median

(IQR)

Agreement

(%)

29. The patient’s use of validated self-assessment scales helps establish appropriate treatment.

8 (2)

84.70

30. The use of the VAS is useful for the health professional in assessing the degree of control of BTcP.

8 (2)

90.58

31. The use of specific scales for the assessment of BTcP (ABPAT scale) is useful for assessing the patient during follow-up.

7 (1)

56.47

32. During follow-up, the emergence of liver failure must be identified as it may affect BTcP control.

7 (1)

68.24

33. During follow-up, the appearance of renal failure must be identified as it may affect BTcP control.

7 (1)

80.00

34. During follow-up, the appearance of mucositis must be identified as it may affect BTcP control.

8 (1)

85.88

35. During follow-up, the appearance of xerostomia must be identified as it may affect BTcP control.

8 (1)

80.00

36. During follow-up, the appearance of bone event must be identified as it may affect BTcP control.

8 (1)

80.00

37. During follow-up, the appearance of fever must be identified as it may affect BTcP control.

7 (2)

57.65

38. During follow-up, the appearance of depression must be identified as it may affect BTcP control.

7 (2)

75.30

39. During follow-up, the evolution of cancer (progression or response) must be assessed as it may affect BTcP control.

8 (2)

94.12

40. New concomitant treatments recently introduced to the treatment of BTcP should be evaluated.

8 (2)

92.94

41. It is important to evaluate the possible interactions of any other concomitant treatment in order to optimize the treatment of BTcP.

8 (2)

95.30

42. In the following follow-up visits, the number of BTcP episodes per day should be assessed.

9 (1)

97.64

43. In the following follow-up visits, the characteristics of BTcP must be assessed (duration, intensity, irradiation, interference with activities of daily living, factors that alleviate or aggravate it).

9 (2)

92.94

44. In the following follow-up visit, it is necessary to assess pain control episodes of BTcP.

9 (1)

100.00

45. In the following follow-up visits, it is necessary to assess the need to repeat doses due to poor control of BTcP.

9 (1)

96.47

46. In the following follow-up visit, it is necessary to assess adherence to pain treatment.

9 (1)

96.47

47. In the following follow-up visits it is necessary to assess how the patient “controls” the appearance of their pain episodes.

8 (1)

92.95

48. The most important adverse event to take into account in the management of patients undergoing treatment for BTcP is constipation.

8 (2)

75.29

49. The most important adverse event to take into account in the management of patients undergoing treatment for BTcP is nausea.

7 (2)

67.06

50. The most important adverse event to take into account in the management of patients undergoing treatment for BTcP is mental confusion.

7 (1)

68.23

51. The most important adverse event to take into account in the management of patients undergoing treatment for BTcP is pruritus.

3 (3)

4.71

52. The most important adverse event to take into account in the management of patients undergoing treatment for BTcP is dyspnea.

3 (2)

7.06

53. The most important adverse event to take into account in the management of patients undergoing treatment for BTcP is immunosuppression.

2 (2)

1.18

54. The most important adverse event to take into account in the management of patients undergoing treatment for BTcP is urinary retention.

6 (3)

31.77

55. The most important adverse event to take into account in the management of patients undergoing treatment for BTcP is delirium.

7 (1)

61.17

56. The most important adverse event to take into account in the management of patients undergoing treatment for BTcP is dizziness.

7 (3)

68.23

57. The most important adverse event to take into account in the management of patients undergoing treatment for BTcP is diaphoresis.

5 (3)

16.47

58. The opioid doses of the basal treatment should be increased when the patient has 4 episodes of BTcP per day.

8 (2)

78.82

59. The opioid doses of the basal treatment should be increased when the patient has more than 4 episodes of BTcP per day.

8 (1)

92.95

60. When an end-of-dose failure is identified, the dose of basal opioid treatment must be increased (An end-of-dose failure is one that occurs before or around the time prescribed for analgesia. This failure is more gradual in onset and longer in duration than the previous ones. It is usually the result of an inadequate analgesic dose or a prolonged administration interval).

7 (2)

69.42

61. When serious adverse events occur during the treatment of BTcP, the dose of opioids should be reduced.

8 (3)

75.30

62. In case of poor tolerance to the treatment of BTcP, it is necessary to change between different pharmaceutical forms of opioids (transdermal patch, solution for injection, nasal spray, or buccal tablets).

8 (2)

89.41

63. In case of inefficiency, it is necessary to change between different presentations of opioids.

8 (2)

78.83

64. Adjuvant treatments can help control BTcP.

8 (1)

94.12

65. It is necessary to add adjuvant medication to minimize opioid doses.

7 (1)

81.18

66. Consideration should be given to possible opioid abuse behaviors.

8 (2)

88.23

ABPAT, Alberta Breakthrough Pain Assessment Tool; BTcP, breakthrough cancer pain; IQR, interquartile range; VAS, Visual Analog Scale

Topic 1: When to Perform the First and Subsequent BTcP Treatment Evaluations

Panelists agreed most of the items proposed about when to perform the first and subsequent BTcP treatment evaluations (items 1–11) (Table 1). Almost all experts agreed that more frequent visits should be done after detecting poor control of BTcP (98.82% of panelists scored in the 7–9 range). Other items with a wide agreement include considering the first follow-up visit 48–72 h after the start of BTcP treatment (88.24% of panelists agreed) and using telephone follow-up of patients with BTcP when resources are available (85.88% of panelists agreed). However, experts did not show agreement or disagreement to carry out the first follow-up visit by telephone (56.46% of panelists agreed), or to consider more frequent visits in patients with impaired liver function (56.47% of panelists agreed).

Topic 2: What to Assess at the First Follow-up Visit and how

All items related to what to assess at the first follow-up visit (items 12–18) reached consensus in most of panelists, such as the number of BTcP episodes per day (98.82% of panelists scored in the 7–9 range), the need to adjust doses due to poor control of BTcP (98.83% of panelists agreed), or the control of pain episodes (97.65% of panelists agreed) (Table 1).

Regarding the items related to what adverse events should be considered in the first follow-up visit of patients under treatment for BTcP (items 19–28), panelists only considered taking into account constipation, nausea, mental confusion, dizziness, and delirium (> 70% of panelists agreed). On the other hand, all experts disagreed to consider immunosuppression at the first follow-up visit. Pruritus, dyspnea, urinary retention, or diaphoresis did not achieve consensus (Table 1).

Topic 3: What to Assess in the Following Visits and how

This topic includes several groups of items that could be explained separately (Table 2). Most panelists agreed that the use of validated scales, either by the patient (self-assessment) or by the health professional (Visual Analog Scale [VAS]), will help in assessing the degree of control of BTcP and stablishing the most appropriate treatment (items 29 and 30; > 84% of panelists scored in the 7–9 range). Experts did not achieve consensus to consider the use of specific scales for the assessing of BTcP during the follow-up, such as the ABPAT (item 31).

A great proportion of panelists agreed that several adverse events may affect the control of BTcP and must be identified during the follow-up visits (items 32–39). These adverse events include liver failure, renal failure, mucositis, xerostomia, bone events, depression, and the evolution of cancer (progression or response) (> 68% of panelists agreed). However, fever did not get enough level of agreement to achieve consensus.

Most panelists agreed that concomitant treatments recently introduced for the treatment of BTcP should be evaluated (item 40; 92.94% of panelists agreed), including the appearance of possible interactions in order to optimize the treatment of BTcP (item 41; 95.30% of panelists agreed).

All items related to what to assess in the follow-up visits reached consensus (items 42–47). Panelists agreed to assess the number of BTcP episodes per day, the characteristics of BTcP, the pain control, the need to repeat doses due to poor control of BTcP, the adherence to pain treatment, and how the patient controls the appearance of pain episodes (> 92% of panelists agreed).

As with the items about the first follow-up visit, panelists did not agree which adverse events must be taken into account during the follow-up visits (items 48–58). Only constipation, nausea, mental confusion, and dizziness were agreed by more than 67% of panelists. In the same way, immunosuppression was disagreed by 98.82% of experts as the most important adverse event to take into account in the management of patients with BTcP. Pruritus, dyspnea, urinary retention, delirium, or diaphoresis did not achieve consensus.

Regarding the use of opioids for the treatment of BTcP (items 58–66), all items proposed reached consensus in agreement. Panelists agreed that the dose of opioids should be increased when the patient has 4 or more episodes of BTcP per day (> 78% of panelists agreed) or when an end-of-dose failure is identified (69.42% of panelists agreed). On the other hand, they agreed that the dose of opioids should be reduced if serious adverse events occur during BTcP treatment (75.30% of panelists agreed). In addition, they considered that it is necessary to change between different pharmaceutical forms of opioids in case of poor tolerance to the treatment (89.41% of panelists agreed) or inefficiency of the therapy (78.83% of panelists agreed). Most of the experts agreed that adjuvant treatment can help in the control of BTcP and to minimize opioid doses (> 78% of panelists agreed). Moreover, panelists thought that consideration should be given to possible opioid abuse behaviors (88.23% of panelists agreed).

Discussion

In general, the opinion of the participating experts on the follow-up of patients with BTcP under opioid treatment was largely uniform, as suggested by the high degree of consensus reached in more than 80% of the items proposed.

Two previous Spanish Delphi consensus ascertain the level of agreement among cancer pain specialists with the optimal definition, diagnosis, and management of BTcP, including a little section about BTcP follow-up [16, 17]. The experts surveyed agreed that patients and adverse events should be assessed after starting BTcP medication within 48–72 h [17]. In addition, experts recommended that the first contact with the patient (including by telephone) should be performed within the first 48 h following the initiation/titration period, and follow-up of patients should be done simultaneously to the scheduled visits and/or whenever requested by the patient [16]. Our panelists also agreed that the first follow-up visit should be done at 48–72 h after starting BTcP treatment, and should coincide with regular medical visits. However, they considered that the first follow-up visit should preferably be face-to-face, using telephone only when BTcP is well controlled or when patients have problems to attend the consultation.

The most agreed items in our study include increase the number of visits after detecting poor control of BTcP, adjust treatment dose due to poor control of BTcP, and assess pain control episodes of BTcP in the first and following visits. All these items have in common the control of BTcP. Some guidelines suggest that the occurrence of 3 to 4 BTcP episodes per day is an acceptable outcome if pain is controlled during the rest of the day [3, 4, 18]. However, this broad generalization deserves reconsideration due to the heterogeneity of BTcP [19, 20]. For example, many BTcP episodes caused by bone metastases may occur more or less frequently depending on the patient’s level of activity [20].

There are several questionnaires and patient-related instruments to assess pain control [7, 8]. However, our panelists prefer to use VAS [21]. They argued that although specific scales such as ABPAT are useful for assessing the patient during follow-up, they are not used frequently in their clinical practice and require more time to be carried out than VAS.

Our panelists agreed that more frequent visits are needed in patients with impaired renal function but not with impaired liver function. This discrepancy may be due to metabolism of opioids [22, 23, 24]. In fact, the European Palliative Care Research Collaborative opioid guidelines project only recommends fentanyl in the first-line and alfentanil in the second-line in patients with an estimated glomerular filtration rate (eGFR) < 30 ml/min [23]. In the same way, the European Association for Palliative Care (EAPC) recommends lower doses of fentanyl, buprenorphine, or methadone in these patients [24]. These strict recommendations may have led our panelists to choose renal impairment and not hepatic impairment as a factor to be considered in order to increase the number of visits to patients with BTcP.

Panelists of our study did not agree that all proposed adverse events must be considered during the first and following visits. According to the summary of product characteristics (SmPC) of opioids, some adverse events are common, such as nausea and dyspnea, but others such as pruritus are rare [25]. However, panelists considered that many of such adverse events could be due more to the cancer disease than to the treatment. Before modifying analgesic treatment as a consequence of an adverse event, they argued that other causes different from treatment must be ruled out previously. Moreover, although it is known the potential of opioids to suppress the immune response and thereby to increase the vulnerability for infections [26], almost all panelists disagreed and argued that such adverse event is not common in their clinical practice or emerged as a consequence of chemotherapy.

According to rapid-onset opioids SmPC, dose should be adjusted if patients consistently present more than four BTcP episodes per day [25]. However, our panelists agreed that opioid doses should be increased when the patient has 4 episodes or more. They consider that patients’ reports of pain episodes are not precise.

Panelists of our study agreed that consideration should be given to possible opioid abuse behaviors. However, although a stricter control measure of opioids might result in the prevention of misuse, barriers in the use of these drugs may drive to a lower use and a poor control of pain. In fact, there are large disparities in the use of opioids to control BTcP in Europe and worldwide [27]. These disparities may be due to affordability of the drug in each country or even the control measures established by the national legislations and regulations of countries [28]. This highlights the need to take adequate measures to prevent aberrant opioid-induced behaviors when treating BTcP in patients with cancer.

The limitations of this study are the same that those of studies with similar design. To minimize the influence of the promotor of consensus exercise, sponsors were not involved in the study. It is important to note that the conclusions of the study are subjective and must be taken with caution to be extrapolated to the clinical practice.

This modified Delphi procedure successfully reached consensus from a panel of medical oncologists in the management of patients with BTcP. Based on their opinions and experience, the main recommendations extracted from the results included:
  • The first follow-up visit should preferably be face-to-face. Subsequently, in some cases, telephone follow-up may be carried out. More frequent visits should be done after detecting poor control of BTcP.

  • In the first and subsequent follow-up visits should be assessed: the number of BTcP episodes per day, the characteristics of BTcP (such as duration or intensity), control of pain episodes, adherence to treatment, how the patient register BTcP episodes, and adverse events that may affect BTcP control and response to treatment.

  • The use of an easy and quick to use scale is useful in the assessment of BTcP, such as VAS.

  • Opioid doses should be increased when patient has ≥ 4 BTcP episodes per day.

  • Opioid doses should be reduced if serious adverse events occur during BTcP treatment.

  • It is necessary to change between different pharmaceutical forms of opioids in case of inefficiency or poor tolerance to the treatment.

  • Adjuvant treatment can help in the control of BTcP and to minimize opioid doses.

In conclusion, this Delphi consensus is of particular relevance, and highlights the different points of view of medical oncologists regarding the follow-up of patients with BTcP under opioid treatment. Nonetheless, the conclusions reached can facilitate the optimization of the monitoring of these patients and promote long-term effectiveness of BTcP control.

Notes

Acknowledgments

The authors wish to thank the Research Unit at Luzán 5 (Madrid) for the design and coordination assistance; Fundación para la Excelencia y la Calidad de la Oncología (ECO) foundation as the project promoter; and Dr. Fernando Sánchez Barbero for the support on the preparation of this manuscript.

Author Contributions

All authors were equally responsible for developing the Delphi survey, coordinating the study, interpreting the results, and revise and approve the final manuscript.

Funding

This study was funded by Kyowa Kirin Farmacéutica S.L.U., through the ECO Foundation.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

This article does not contain any study with human participants or animals performed by any of the authors. Anonymity of the panelists who completed the questionnaire was guaranteed. The study was approved by the Clinical Research Ethics Committee of the Hospital Clínico San Carlos (Madrid, Spain).

Informed Consent

Informed consent for this study is not necessary. Due to the Delphi methodology, which guarantees the anonymity of the panelists who completed the questionnaire, it was not necessary to obtain a consent report from them. No patients participated in the study.

Supplementary material

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ESM 1 (DOCX 14 kb)

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • José Luis Larriba González
    • 1
    Email author
  • Diego Cayuela López
    • 2
  • Ovidio Fernández Calvo
    • 3
  • Salvador Garcerá Juan
    • 4
  • Raquel Molina Villaverde
    • 2
    • 5
  • Juan José Reina Zoilo
    • 6
  • Vicente Guillém
    • 7
  • Carlos Camps
    • 8
  • Margarita Feyjóo
    • 9
  1. 1.Servicio de Oncología Médica, Hospital Clínico San Carlos Departamento de MedicinaUniversidad ComplutenseMadridSpain
  2. 2.Servicio de Oncología MédicaHospital de ManacorManacorSpain
  3. 3.Servicio de Oncología MédicaComplejo Hospitalario Universitario de OrenseOrenseSpain
  4. 4.Servicio de Oncología MédicaHospital de ManisesManisesSpain
  5. 5.Hospital Universitario Príncipe AsturiasAlcalá de HenaresSpain
  6. 6.Servicio de Oncología MédicaHospital Universitario Virgen MacarenaSevillaSpain
  7. 7.Fundación ECO, Servicio de Oncología MédicaInstituto Valenciano de OncologíaValenciaSpain
  8. 8.Fundación ECO, Servicio de Oncología Médica, Hospital General UniversitarioUniversidad de ValenciaValenciaSpain
  9. 9.Fundación ECO, Servicio de Oncología MédicaHospital Sanitas La MoralejaMadridSpain

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