Multidimensional Statistical Technique for Interpreting the Spontaneous breakthrough Cancer Pain Phenomenon. A Secondary Analysis from the IOPS-MS Study

Breakthrough cancer pain (BTcP) is a temporary exacerbation of pain that "breaks through" a phase of adequate pain control by an opioid-based therapy. The non-predictable BTcP (NP-BTcP) is a subtype of BTcP that occurs in the absence of any specific activity. Since NP-BTcP has an important clinical impact, this analysis is aimed at characterizing the NP-BTcP phenomenon through a multidimensional statistical technique. This is a secondary analysis based on the Italian Oncologic Pain multiSetting - Multicentric Survey (IOPS-MS) . A correlation analysis was performed to characterize NP-BTcP profile about its intensity, number of episodes per day, and type. The Multidimensional Correspondence Analysis (MCA) determined the identification of 4 groups (Phenotypes). A univariate analysis was performed to assess differences between the 4 Phenotypes and selected covariates. The four phenotypes represent the hierarchical classification according to the status of NP-BTcP: from the best (Phenotype 1) to the worst (Phenotype 4). The univariate analysis found a significant association between the onset time &gt;10 min in the Phenotype 1 (37.3%) vs. the onset ≤ 10 min in Phenotype 4 (74.2%) (p&lt;0.001). The Phenotype 1 was characterized by gastrointestinal type of cancer (26.4%) respect to Phenotype 4 where the most frequent cancer affected the lung (28.8%) (p&lt;0.001). Phenotype 4 was mainly managed with rapid onset opioids, while in Phenotype 1 many patients were treated with oral, subcutaneous, or intravenous morphine (56.4% and 44.4%, respectively; p=0.008). The ability to characterize NP-BTcP can offer enormous benefits for the management of this serious aspect of cancer pain. This strategy can provide many indications for identifying the diagnostic and therapeutic gaps on NP-BTcP management.

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Multidimensional Statistical Technique for Interpreting the Spontaneous Breakthrough Cancer Pain Phenomenon. A Secondary Analysis from the IOPS-MS Study

Cancers ◽

10.3390/cancers13164018 ◽

2021 ◽

Vol 13 (16) ◽

pp. 4018

Author(s):

Marco Cascella ◽

Anna Crispo ◽

Gennaro Esposito ◽

Cira Antonietta Forte ◽

Sergio Coluccia ◽

...

Keyword(s):

Cancer Pain ◽

Specific Activity ◽

Multiple Correspondence Analysis ◽

Univariate Analysis ◽

Secondary Analysis ◽

Hierarchical Classification ◽

Onset Time ◽

Rapid Onset ◽

Statistical Technique ◽

Breakthrough Cancer Pain

Breakthrough cancer pain (BTcP) is a temporary exacerbation of pain that “breaks through” a phase of adequate pain control by an opioid-based therapy. The non-predictable BTcP (NP-BTcP) is a subtype of BTcP that occurs in the absence of any specific activity. Since NP-BTcP has an important clinical impact, this analysis is aimed at characterizing the NP-BTcP phenomenon through a multidimensional statistical technique. This is a secondary analysis based on the Italian Oncologic Pain multiSetting—Multicentric Survey (IOPS-MS). A correlation analysis was performed to characterize the NP-BTcP profile about its intensity, number of episodes per day, and type. The multiple correspondence analysis (MCA) determined the identification of four groups (phenotypes). A univariate analysis was performed to assess differences between the four phenotypes and selected covariates. The four phenotypes represent the hierarchical classification according to the status of NP-BTcP: from the best (phenotype 1) to the worst (phenotype 4). The univariate analysis found a significant association between the onset time >10 min in the phenotype 1 (37.3%)’ vs. the onset > 10 min in phenotype 4 (25.8%) (p < 0.001). Phenotype 1 was characterized by the gastrointestinal type of cancer (26.4%) with respect to phenotype 4, where the most frequent cancer affected the lung (28.8%) (p < 0.001). Phenotype 4 was mainly managed with rapid-onset opioids, while in phenotype 1, many patients were treated with oral, subcutaneous, or intravenous morphine (56.4% and 44.4%, respectively; p = 0.008). The ability to characterize NP-BTcP can offer enormous benefits for the management of this serious aspect of cancer pain. Although requiring validation, this strategy can provide many indications for identifying the diagnostic and therapeutic gaps in NP-BTcP management.

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Factors influencing the use of opioids for breakthrough cancer pain: A secondary analysis of the IOPS‐MS study

European Journal of Pain ◽

10.1002/ejp.1339 ◽

2018 ◽

Vol 23 (4) ◽

pp. 719-726 ◽

Cited By ~ 4

Author(s):

Sebastiano Mercadante ◽

Claudio Adile ◽

Francesco Masedu ◽

Paolo Marchetti ◽

Andrea Costanzi ◽

...

Keyword(s):

Cancer Pain ◽

Secondary Analysis ◽

Breakthrough Cancer Pain ◽

Factors Influencing

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Proportional dose of rapid-onset opioid in breakthrough cancer pain management

Medicine ◽

10.1097/md.0000000000011593 ◽

2018 ◽

Vol 97 (30) ◽

pp. e11593 ◽

Cited By ~ 4

Author(s):

Tsung-Yu Yen ◽

Jeng-Fong Chiou ◽

Wei-Yong Chiang ◽

Wen-Hao Su ◽

Ming-Yuan Huang ◽

...

Keyword(s):

Pain Management ◽

Cancer Pain ◽

Rapid Onset ◽

Cancer Pain Management ◽

Breakthrough Cancer Pain

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Breakthrough cancer pain clinical features and differential opioids response: A machine learning approach in 4,016 cancer patients of IOPS-MS study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e24150 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e24150-e24150

Author(s):

Francesco Pantano ◽

Paolo Manca ◽

Grazia Armento ◽

Tea Zeppola ◽

Angelo Onorato ◽

...

Keyword(s):

Cancer Pain ◽

Clinical Features ◽

Learning Algorithm ◽

Optimal Dose ◽

Rapid Onset ◽

Optimal Number ◽

Breakthrough Cancer Pain ◽

Partitioning Around Medoids ◽

Linear Relationships ◽

Practice Methods

e24150 Background: A large proportion of patients with cancer suffer from Breakthrough cancer pain (BTcP). Several unmet clinical needs concerning BTcP treatment, like optimal opioids dosage, are being investigated. We explored with an unsupervised learning algorithm whether distinct subtypes of BTcP exist and whether they can provide new insights into clinical practice. Methods: We used partitioning around medoids algorithm on a large dataset of patients with BTcP previously collected by the IOPS group in order to identify possible subgroups of BTcP; the input of the algorithm consisted of different BTcP features, like its duration or its intensity. Silhouette statistics was used to pick an optimal number of clusters. Resulting clusters were analyzed in terms of BTcP therapy satisfaction, clinical features and usage of basal pain and rapid onset opioids. Opioids dosages were converted to a unique scale and BTcP-opioids-to-basal-pain-opioids ratio (OpR) was calculated for each patient. Polynomial logistic regression was used to catch non-linear relationships between therapy satisfaction and opioids usage. Results: The cohort comprised 4016 patients with controlled basal pain and suffering from BTcP. Our algorithm identified 12 distinct BTcP clusters. Optimal OpRs differed across the clusters, ranging from 15% to 50%. In the whole cohort, OpR was more clearly associated with therapy satisfaction compared with BTcP opioids or basal pain opioids alone. The majority of the clusters were linked to peculiar association of certain drugs with therapy satisfaction or dissatisfaction. A free online tool was created for new patients cluster computation ( https://mancapaolo.shinyapps.io/UCBM_BTcPclusters/ ) in order to validate these clusters in future studies and to provide a possible, handy indications for personalized BTcP therapy. Conclusions: This work proposes a classification for BTcP and identifies subgroups of patients with unique efficacy of different pain medications. This work supports the theory that the optimal dose of BTcP opioids depends on the dose of basal opioids and identifies novel values, possibly useful for future trials.

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Oral transmucosal opioids

Cancer-related Breakthrough Pain ◽

10.1093/med/9780198840480.003.0006 ◽

2019 ◽

pp. 55-72

Author(s):

Andrew Davies

Keyword(s):

Drug Delivery ◽

Cancer Pain ◽

Oral Mucosa ◽

Rapid Onset ◽

Sublingual Administration ◽

Technical Equipment ◽

Breakthrough Cancer Pain ◽

Passive Absorption ◽

Transmucosal Administration

The oral transmucosal routes are buccal and sublingual. The absorption of drugs across the oral mucosa involves a process of passive absorption, and may involve either the transcellular route or the paracellular route. A number of drug factors affect the absorption of drugs across the oral mucosa. Oral transmucosal drug delivery does not require expertise, preparation, or technical equipment. Oral transmucosal administration may be associated with rapid onset of analgesia. A number of fentanyl-based formulations are commercially available to manage breakthrough cancer pain. A variety of other opioids have been subject to oral transmucosal administration. However, many of these opioids are not very lipophilic and, therefore, not suited for buccal or sublingual administration. Some of the more successful ones are alfentanil and sufentanil.

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Intranasal and intrapulmonary opioids

Cancer-related Breakthrough Pain ◽

10.1093/med/9780198840480.003.0007 ◽

2019 ◽

pp. 73-82

Author(s):

Andrew Davies

Keyword(s):

Cancer Pain ◽

Intranasal Administration ◽

Rapid Onset ◽

Dry Powder Inhalers ◽

Metered Dose Inhalers ◽

Breakthrough Cancer Pain ◽

Inhalation Devices ◽

Metered Dose ◽

Specialized Equipment ◽

Transdermal Route

The intranasal and intrapulmonary routes are simple, do not necessarily require any specialized equipment, and can be used by both patients and their non-professional caregivers. Intranasal administration may be associated with rapid onset of analgesia. A number of fentanyl-based formulations are commercially available to manage breakthrough cancer pain. Intranasal opioids can be delivered by traditional spray bottles, and also by syringes fitted with atomisers. The intrapulmonary route has the potential for rapid onset of analgesia. and can be delivered by traditional nebulizers, and other inhalation devices (e.g. metered dose inhalers, dry powder inhalers). The transdermal route has less potential for rapid onset of analgesia. However, new patch technology (iontophoretic technology) may alter the current position.

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Breakthrough Cancer Pain Clinical Features and Differential Opioids Response: A Machine Learning Approach in Patients With Cancer From the IOPS-MS Study

JCO Precision Oncology ◽

10.1200/po.20.00158 ◽

2020 ◽

pp. 1339-1349

Author(s):

Francesco Pantano ◽

Paolo Manca ◽

Grazia Armento ◽

Tea Zeppola ◽

Angelo Onorato ◽

...

Keyword(s):

Cancer Pain ◽

Clinical Features ◽

Learning Algorithm ◽

Large Data ◽

Optimal Dose ◽

Rapid Onset ◽

Opioid Use ◽

Data Set ◽

Breakthrough Cancer Pain ◽

Patients With Cancer

PURPOSE A large proportion of patients with cancer suffer from breakthrough cancer pain (BTcP). Several unmet clinical needs concerning BTcP treatment, such as optimal opioid dosages, are being investigated. In this analysis the hypothesis, we explore with an unsupervised learning algorithm whether distinct subtypes of BTcP exist and whether they can provide new insights into clinical practice. METHODS Partitioning around a k-medoids algorithm on a large data set of patients with BTcP, previously collected by the Italian Oncologic Pain Survey group, was used to identify possible subgroups of BTcP. Resulting clusters were analyzed in terms of BTcP therapy satisfaction, clinical features, and use of basal pain and rapid-onset opioids. Opioid dosages were converted to a unique scale and the BTcP opioids-to-basal pain opioids ratio was calculated for each patient. We used polynomial logistic regression to catch nonlinear relationships between therapy satisfaction and opioid use. RESULTS Our algorithm identified 12 distinct BTcP clusters. Optimal BTcP opioids-to-basal pain opioids ratios differed across the clusters, ranging from 15% to 50%. The majority of clusters were linked to a peculiar association of certain drugs with therapy satisfaction or dissatisfaction. A free online tool was created for new patients’ cluster computation to validate these clusters in future studies and provide handy indications for personalized BTcP therapy. CONCLUSION This work proposes a classification for BTcP and identifies subgroups of patients with unique efficacy of different pain medications. This work supports the theory that the optimal dose of BTcP opioids depends on the dose of basal opioids and identifies novel values that are possibly useful for future trials. These results will allow us to target BTcP therapy on the basis of patient characteristics and to define a precision medicine strategy also for supportive care.

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The reasons and timing of the oral transmucosal fentanyl administration in Japan.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e21665 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e21665-e21665

Author(s):

Shinya Kajiura ◽

Tatsuhiko Kashii ◽

Akiyoshi Takaki ◽

Shingo Chikaoka ◽

Naomi Hayashi ◽

...

Keyword(s):

Cancer Pain ◽

Breakthrough Pain ◽

Rapid Onset ◽

University Hospital ◽

Aggressive Treatment ◽

Fentanyl Patch ◽

Oral Medicine ◽

Breakthrough Cancer Pain ◽

Chemotherapy Administration ◽

Ecog Ps

e21665 Background: The oral transmucosal fentanyl disintegrating tablet, Abstral, is a formulation by which fentanyl can be rapidly absorbed across the oral mucosa producing rapid onset analgesia, and which may be effective for breakthrough cancer pain. It can be administered for the patients who cannot take the oral medicine. It has been marketed since 2014 in Japan. Methods: We selected patients who were administered Abstral for breakthrough cancer pain between 2014 and 2016 at Toyama University Hospital in Japan. We retrospectively investigated administration reasons based on medical record of those patients. Results: There were 111 patients who were administered Abstral. Primary lesions of lung/Gastrointestin/others were 43/52/16, respectively. ECOG PS 0-2/3-4 were 27/84, respectively. The median age was 66 y.o. (range 35-91 y.o.). Regularly using opioid were fentanyl patch prescribed for all patients. Median dose of fentanyl patch was 25mcg/hr (range 12.5-250mcg/hr). 90 patients (81%) had difficulties in the administration of oral medicine, which was the main reason of Abstral administration. Four patients (4%) were to reduce constipation and vomiting as side effects of oxycodone. Seven patients (6%) were to start a fentanyl patch. Three patients (3%) were assessed poor effect for short-acting opioid. Only seven patients (6%) were expected of rapid onset of analgesia effect. Abstral was administered in 27 patients (24%) during aggressive treatment such as chemotherapy administration and in 84 patients (76%) after aggressive treatment. Conclusions: The oral transmucosal fentanyl was administered for the patients who cannot take the oral medicine in Japan while it is expected to be administered to those who want to relieve breakthrough pain fast. Affirming a common understanding of the efficacy of the oral transmucosal fentanyl and breakthrough cancer pain is necessary in Japan.

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