Special Issue "Cancer Pains"

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 January 2019)

Special Issue Editor

Guest Editor
Prof. Dr. Sebastiano Mercadante

Supportive/Palliative Care Unit, La Maddalena Cancer Center, 90146 Palermo, Italy
Website | E-Mail
Interests: Supportive care in oncology, palliative care, cancer pain, symptom management, end of life

Special Issue Information

Dear Colleagues,

Pain is one of the most prevalent, burdensome, and feared symptoms among cancer patients.   The prevalence of pain in cancer population has been estimated to be high, particularly in the advanced stage of disease. In developing countries, pain prevalence is even higher due to a late diagnosis. On the other hand chronic pain in cancer survivors affect about 1/3 of patients.

With such high figures, attention to pain should considered an institutional priority for oncology setting. While scientific evidence and effort to disseminate them through recommendations and guidelines, suboptimal management of pain persist in clinical setting, with over 80% of the world’s population being inadequately treated.

The pharmacologic treatment with analgesics is the foundation of cancer pain management. Despite the lack of significant evidence of effectiveness and potential adverse consequences, opioids are recommended as the mainstay of treatment for cancer pain.

     Unfortunately many barriers regarding the use of opioids persist. Despite the changes in attitudes in the medical community, outdated rules and regulations aimed, at limiting criminal behavior, abuse and addiction, remain and propagate the legacy of fear about opioids. Patients and relatives often hamper their own treatment due to similar misconceptions about opioids, nonadherence to treatment regimens, and poor communication of their concerns. Cultural barriers and lack of knowledge are a further limiting factor for the appropriate use of opioids. Experts in the field will prepare leading articles regarding the pain classification, neuropathic pain, interventional techniques, and difficult pain syndromes. We aim to stimulate discussion by bringing together expert opinion and new science from across the field in a Special Issue of Cancers. We welcome submissions that cover relevant topics of cancer pain management.

Prof. Dr. Sebastiano Mercadante
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (8 papers)

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Research

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Open AccessArticle The Circadian Rhythm of Breakthrough Pain Episodes in Terminally-ill Cancer Patients
Received: 16 November 2018 / Revised: 17 December 2018 / Accepted: 20 December 2018 / Published: 24 December 2018
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Abstract
Opioid therapy must be adjusted to the rhythm of a cancer patient’s pain to ensure adequate symptom control at the end of life (EOL). However, to-date no study has explored the rhythm of breakthrough pain (BTP) episodes in terminally-ill cancer patients. This prospective [...] Read more.
Opioid therapy must be adjusted to the rhythm of a cancer patient’s pain to ensure adequate symptom control at the end of life (EOL). However, to-date no study has explored the rhythm of breakthrough pain (BTP) episodes in terminally-ill cancer patients. This prospective longitudinal study was aimed at verifying the existence of a circadian rhythm of BTP episodes in terminally-ill cancer patients. Consecutive adult cancer patients at their EOL treated with long-acting major opioids to control background pain (Numeric Rating Scale ≤ 3/10) were recruited from two Italian palliative care services. Using a personal diary, patients recorded the frequency and onset of BTP episodes and the analgesic rescue therapy taken for each episode over a 7-day period. Rhythms identified in BTP episodes were validated by Cosinor analysis. Overall, 101 patients were enrolled; nine died during the study period. A total of 665 BTP episodes were recorded (average of 7.2 episodes, mean square error 0.8) per patient, with 80.6% of episodes recorded between 8:00 a.m. and 12:00 a.m. At Cosinor analysis, a circadian rhythm of BTP episodes was observed, with a Midline Estimating Statistics of the Rhythm (MESOR) of 1.5, a double amplitude of 1.8, and an acrophase at 12:30 p.m. (p < 0.001). Oral morphine was the most frequent analgesic rescue therapy employed. In terminally-ill cancer patients, BTP episodes follow a circadian rhythm; thus, tailoring the timing of opioid administration to this rhythm may prevent such episodes. This circadian rhythm of BTP episodes in terminally-ill cancer patients should be confirmed in larger samples. Full article
(This article belongs to the Special Issue Cancer Pains)
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Open AccessArticle Pharmacokinetics of Sublingually Delivered Fentanyl in Head and Neck Cancer Patients Treated with Curatively Aimed Chemo or Bioradiotherapy
Cancers 2018, 10(11), 445; https://doi.org/10.3390/cancers10110445
Received: 8 October 2018 / Revised: 9 November 2018 / Accepted: 12 November 2018 / Published: 15 November 2018
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Abstract
Over 90% of patients treated for head and neck cancer with curatively aimed chemo or bioradiotherapy will develop painful mucositis and xerostomia. Sublingually delivered fentanyl (SDL) is a rapid acting opioid to treat breakthrough pain. It is unclear how SDL is absorbed by [...] Read more.
Over 90% of patients treated for head and neck cancer with curatively aimed chemo or bioradiotherapy will develop painful mucositis and xerostomia. Sublingually delivered fentanyl (SDL) is a rapid acting opioid to treat breakthrough pain. It is unclear how SDL is absorbed by the mucosa of these patients. Therefore, the aim of this study was to investigate the effects of mucositis and xerostomia on the absorption of SDL. Thirteen patients who received chemo or bioradiotherapy (RT), were given a single dose of fentanyl: Before start of RT, 3 and 6 weeks after start of RT, and 6 weeks after finishing RT. Pharmacokinetic samples were taken. The primary endpoint was the relative difference (RD) between systemic exposure to fentanyl (area under the curve; AUC) at baseline (AUCbaseline) and fentanyl AUC in the presence of mucositis grade ≥2. The secondary endpoint was the RD between AUCbaseline and fentanyl AUC in the presence of xerostomia, which were analyzed by means of a paired t-test on log-transformed data. Mucositis resulted in a 12.7% higher AUC (n = 13; 95% CI: −10.7% to +42.2%, p = 0.29) compared to baseline levels and xerostomia resulted in a 22.4% lower AUC (n = 8; 95% CI: −51.9% to +25.3%, p = 0.25) compared to baseline levels. Mucositis grade ≥2 or xerostomia caused by chemo or bioradiotherapy does not significantly alter the systemic exposure to SDL. Patients with pain during and after chemo or bioradiotherapy may be safely treated with SDL. Full article
(This article belongs to the Special Issue Cancer Pains)
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Review

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Open AccessReview Cancer Pain Assessment and Classification
Cancers 2019, 11(4), 510; https://doi.org/10.3390/cancers11040510
Received: 30 January 2019 / Revised: 29 March 2019 / Accepted: 3 April 2019 / Published: 10 April 2019
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Abstract
More than half of patients affected by cancer experience pain of moderate-to-severe intensity, often in multiple sites, and of different etiologies and underlying mechanisms. The heterogeneity of pain mechanisms is expressed with the fluctuating nature of cancer pain intensity and clinical characteristics. Traditional [...] Read more.
More than half of patients affected by cancer experience pain of moderate-to-severe intensity, often in multiple sites, and of different etiologies and underlying mechanisms. The heterogeneity of pain mechanisms is expressed with the fluctuating nature of cancer pain intensity and clinical characteristics. Traditional ways of classifying pain in the cancer population include distinguishing pain etiology, clinical characteristics related to pain and the patient, pathophysiology, and the use of already validated classification systems. Concepts like breakthrough, nociceptive, neuropathic, and mixed pain are very important in the assessment of pain in this population of patients. When dealing with patients affected by cancer pain it is also very important to be familiar to the characteristics of specific pain syndromes that are usually encountered. In this article we review methods presently applied for classifying cancer pain highlighting the importance of an accurate clinical evaluation in providing adequate analgesia to patients. Full article
(This article belongs to the Special Issue Cancer Pains)
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Open AccessReview Interventional Techniques for the Management of Cancer-Related Pain: Clinical and Critical Aspects
Cancers 2019, 11(4), 443; https://doi.org/10.3390/cancers11040443
Received: 27 February 2019 / Revised: 14 March 2019 / Accepted: 26 March 2019 / Published: 29 March 2019
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Abstract
Interventional techniques to manage cancer-related pain may be efficient treatment modalities in patients unresponsive or unable to tolerate systemic opioids. However, indication and selection of the right technique demand knowledge, which is still incipient among clinicians. The present article summarizes the current evidence [...] Read more.
Interventional techniques to manage cancer-related pain may be efficient treatment modalities in patients unresponsive or unable to tolerate systemic opioids. However, indication and selection of the right technique demand knowledge, which is still incipient among clinicians. The present article summarizes the current evidence regarding the five most essential groups of interventional techniques to treat cancer-related pain: Neuraxial analgesia, minimally invasive procedures for vertebral pain, sympathetic blocks for abdominal cancer pain, peripheral nerve blocks, and percutaneous cordotomy. Furthermore, indication, mechanism, drug agents, contraindications, and complications of the main techniques of each group are discussed. Full article
(This article belongs to the Special Issue Cancer Pains)
Open AccessReview Personalized Radiation Therapy in Cancer Pain Management
Cancers 2019, 11(3), 390; https://doi.org/10.3390/cancers11030390
Received: 3 February 2019 / Revised: 5 March 2019 / Accepted: 11 March 2019 / Published: 19 March 2019
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Abstract
The majority of advanced cancer patients suffer from pain, which severely deteriorates their quality of life. Apart from analgesics, bisphosphonates, and invasive methods of analgesic treatment (e.g., intraspinal and epidural analgesics or neurolytic blockades), radiation therapy plays an important role in pain alleviation. [...] Read more.
The majority of advanced cancer patients suffer from pain, which severely deteriorates their quality of life. Apart from analgesics, bisphosphonates, and invasive methods of analgesic treatment (e.g., intraspinal and epidural analgesics or neurolytic blockades), radiation therapy plays an important role in pain alleviation. It is delivered to a growing primary tumour, lymph nodes, or distant metastatic sites, producing pain of various intensity. Currently, different regiments of radiation therapy methods and techniques and various radiation dose fractionations are incorporated into the clinical practice. These include palliative radiation therapy, conventional external beam radiation therapy, as well as modern techniques of intensity modulated radiation therapy, volumetrically modulated arch therapy, stereotactic radiosurgery or stereotactic body radiation therapy, and brachytherapy or radionuclide treatment (e.g., radium-223, strontium-89 for multiple painful osseous metastases). The review describes the possibilities and effectiveness of individual patient-tailored conventional and innovative radiation therapy approaches aiming at pain relief in cancer patients. Full article
(This article belongs to the Special Issue Cancer Pains)
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Open AccessReview Cancer-Related Neuropathic Pain
Cancers 2019, 11(3), 373; https://doi.org/10.3390/cancers11030373
Received: 15 February 2019 / Revised: 5 March 2019 / Accepted: 12 March 2019 / Published: 16 March 2019
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Abstract
Neuropathic pain in cancer is common and debilitating. It is important to differentiate neuropathic pain from other cancer-related pains as it is associated with worse pain outcomes and requires different treatment strategies. This review summarises recent updates to pain classification, aetiology, pain assessment [...] Read more.
Neuropathic pain in cancer is common and debilitating. It is important to differentiate neuropathic pain from other cancer-related pains as it is associated with worse pain outcomes and requires different treatment strategies. This review summarises recent updates to pain classification, aetiology, pain assessment and current recommendations for treatment in patients with cancer-related neuropathic pain. Full article
(This article belongs to the Special Issue Cancer Pains)
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Open AccessReview Treatment of Pain in Cancer: Towards Personalised Medicine
Cancers 2018, 10(12), 502; https://doi.org/10.3390/cancers10120502
Received: 8 November 2018 / Revised: 3 December 2018 / Accepted: 7 December 2018 / Published: 10 December 2018
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Abstract
Despite increased attention to cancer pain, pain prevalence in patients with cancer has not improved over the last decade and one third of cancer patients on anticancer therapy and half of patients with advanced disease still suffer from moderate to severe pain. In [...] Read more.
Despite increased attention to cancer pain, pain prevalence in patients with cancer has not improved over the last decade and one third of cancer patients on anticancer therapy and half of patients with advanced disease still suffer from moderate to severe pain. In this review, we explore the possible reasons for the ongoing high prevalence of cancer pain and discuss possible future directions for improvement in personalised pain management. Among possible reasons for the lack of improvement are: Barriers for patients to discuss pain with clinicians spontaneously; pain measurement instruments are not routinely used in daily practice; limited knowledge concerning the assessment of undertreatment; changes in patients’ characteristics, including the ageing of the population; lack of significant improvement in the treatment of neuropathic pain; limitations of pharmacological treatment and lack of evidence-based nonpharmacological treatment strategies. In order to improve cancer pain treatment, we recommend: (1) Physicians proactively ask about pain and measure pain using assessment instruments; (2) the development of an optimal tool measuring undertreatment; (3) educational interventions to improve health care workers’ skills in pain management; (4) the development of more effective and personalised pharmacological and nonpharmacological pain treatment. Full article
(This article belongs to the Special Issue Cancer Pains)
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Other

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Open AccessFeature PaperPerspective The Patient with Difficult Cancer Pain
Cancers 2019, 11(4), 565; https://doi.org/10.3390/cancers11040565 (registering DOI)
Received: 12 March 2019 / Revised: 17 April 2019 / Accepted: 18 April 2019 / Published: 19 April 2019
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Abstract
Most patients with cancer pain can be managed with relatively simple methods using oral analgesics at relatively low doses, even for prolonged periods of time. However, in some clinical conditions pain may be more difficult to manage. Various factors can interfere with a [...] Read more.
Most patients with cancer pain can be managed with relatively simple methods using oral analgesics at relatively low doses, even for prolonged periods of time. However, in some clinical conditions pain may be more difficult to manage. Various factors can interfere with a desirable and favorable analgesic response. Data from several studies assessing factors of negative pain prognosis have indicated that neuropathic pain, incident pain, psychological distress, opioid addiction, and baseline pain intensity were associated with more difficult pain control. In this narrative review, the main factors that make the therapeutic response to opioids difficult are examined. Full article
(This article belongs to the Special Issue Cancer Pains)
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