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R. Malayeri

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    ED06 - Symptom Management in Lung Cancer (ID 269)

    • Event: WCLC 2016
    • Type: Education Session
    • Track: Palliative Care/Ethics
    • Presentations: 6
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      ED06.01 - Causes and Management of Dyspnea (ID 6447)

      16:00 - 17:30  |  Author(s): O. Burghuber

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      Abstract not provided

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      ED06.02 - Endobronchial and Pleural Palliation (ID 6448)

      16:00 - 17:30  |  Author(s): A. Valipour

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      Abstract not provided

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      ED06.03 - Pain Management (ID 6449)

      16:00 - 17:30  |  Author(s): V. Hirsh

      • Abstract
      • Presentation
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      Abstract:
      Introduction Pain is the most common symptom in cancer patients and it is also the most common symptom in lung cancer patients.[1]The majority of patients with lung cancer present with advanced stage of the disease at diagnosis. Symptoms may result from local effects of the tumor, from regional or distant spread or from distant effects not related to metastases-paraneoplastic syndromes. Pain in these patients may be associated with depression, fatigue [2] and may affect quality of life and patients’ performance status. Early palliative care including pain management may increase their survival. [3] Pain can be classified by type of pain or according to the origin of the pain. The location or origin of the pain determines the type of pain, thoracic or extrathoracic. Pain Pain is often multifactorial in origin and needs to be addressed in each aspect. It can be acute or chronic. Acute pain can be caused by hemorrhage into a tumor, bone pain secondary to a pathological fracture, visceral pain, ie. from acute intestinal obstruction or perforation of a viscous. Its duration is limited and predictable. Chronic pain is differentiated by its longevity. It is estimated that approximately 75% of cancer patients live with chronic pain. [4] It must be approached with dual aim: relieving the pain as well as preventing further recurrences of pain. Pathophysiology of Pain Physiological pain is termed nociceptive pain due to the stimulation of the sensory nociceptors located in tissues when damaged. They are somatic, visceral, neuropathic and psychogenic pains. [5] Neuropathic pain is associated with a loss of opioid receptors in sensory afferents and an increased release of glutamate in the dorsal horn. The resultant hyperexcitability causes spontaneous pain and hyperalgesia and allodynia in areas adjacent to the nerve damage. There are three main causes of pain in patients with advanced lung cancer: Skeletal metastatic disease 34%, Pancoast tumor 31%, chest wall disease 21%. [6] Principles of Pain Management The World Health Organization analgesic ladder for cancer pain relief provides a stepwise approach to managing pain in cancer patients. [7] Step 1 includes paracetamol or non-steroidal anti-inflammatory drugs. Step 2- weak opioids, ie. codeine. Step 3- strong opioids, ie. morphine. Non-opioid and adjuvant treatments can be added to steps 2 and 3. Different routes of the administration of analgesics and their side effects management will be described. Their advantages and disadvantages of each route of administration will be pointed out. The need of adjuvant treatments such as tricyclic antidepressants and anticonvulsants, corticosteroids, topical analgesics, treatments of nausea, constipation, etc., are an integral part of pain management. Interventional procedures help reduce the doses of analgesics and their side effects. [8] Special mention will be about skeletal metastases and bone targeted agents such as zoledronic acid and denosumab, which have shown ability to reduce the pain and analgesic consumption in lung cancer patients. [9] Complementary therapies which help to control pain will also be mentioned.ie. Acupuncture,[10] psychological methods of care, etc. Conclusion An active multidisciplinary approach is required to manage pain in patients with advanced lung cancer. Multifactorial pain is frequent and may require several different analgesics, along with general palliative care and even special interventional procedures. Patients with advanced lung cancer live longer as there are more treatment options. It is of utmost importance to preserve a good quality of life with a better performance status to enable them to receive now further available therapies. [1] Caraceni A, Portenoy RK. An international survey of cancer pain characteristics and syndromes. IASP Task Force on Cancer Pain. Pain. 1999;82 (32) :263-74. [2] Laird BJ, Scott AC, Colvin LA, et al. Pain, depression, and fatigue as a symptom cluster in advanced cancer. J. Pain Symptom Manage. 2011;42(1): 1-11. [3] Temel JS, Greer JA, Muzikansky A, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med. 2010;363(8):733-42. [4] Ferrell BR, Juarez G. Borneman T. Use of routine and breakthrough analgesia in care. Oncol Nurs Forum. 1999;26(10):1655-61. [5] Portenoy RK, Lesage P. Management of cancer pain. Lancet. 1999;353 (9165):1695-700. [6] Watson PN, Evans RJ. Intractable pain with lung cancer. Pain. 1987; 29(2):163-73. [7] Geneva W. World Health Organisation. Cancer Pain Relief. 1996 [8] Vranken JH, Zuurmond WW, de Lange JJ. Continuous brachial plexus block as treatment for the Pancoast syndrome. Clin J Pain . 2000;16(4):327-33 [9] Rosen LS, Gordon D, Tchekmedyian S, et al. Zoledronic acid versus placebo in the treatment of skeletal metastases in patient with lung cancer and other solid tumors: a phase III, double-blind, randomized trial—the Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group. J Clin Oncol. 2003;21(16):3150-7. [10] Cassileth BR, Deng GE, Gomez JE, Johnstone PA, Kumar N, Vickers AJ. Complementary therapies and integrative oncology in lung cancer. ACCP evidence-based clinical practice guidelines (2[nd] edition). Chest. 2007;132(Suppl3):340S-54.

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      ED06.04 - Biology and Management of Tumor Cachexia (ID 6450)

      16:00 - 17:30  |  Author(s): J. Crawford

      • Abstract
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      Abstract:
      The International Consensus Conference definition of cancer cachexia is a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass with or without fat mass that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment.[1] As clinicians, we define cachexia clinically based on weight loss of 5% or greater or body mass index <20 kg/m[2], with 2% weight loss. On physical exam, we recognize cachexia based on gross loss of muscle mass and weakness, often associated with physical findings such as temporal wasting. However, these patients with physical stigmata of cachexia are a small subgroup of the total population. If one assesses objective measures of muscle mass, approximately half of patients with advanced lung cancer will have muscle wasting at diagnosis and 2/3 of patients will develop it during their treatment course. This muscle wasting or sarcopenia, occurs across all weight groups, including those with normal weight, overweight and obesity.[2] These patients would not be recognized clinically to be cachetic. Yet, they have significant clinical consequences from muscle wasting. The use of standardized CT for the quantitative assessment of skeletal muscle and other body tissues has helped us better understand the importance of muscle and its impact on cancer outcomes.[3] Muscle wasting is associated with an increased risk of dose limiting chemotherapy toxicity, shorter time to disease progression and reduced overall survival. Clinically, the cancer patient with cachexia undergoes a progressive decline in muscle mass with associated anorexia, fatigue and reduced quality of life. Patient reported outcomes include weakness, declining muscle strength, reduced mobility and impact on physical performance. At a molecular level, this loss of muscle mass is associated with a number of biochemical changes in enzymes, regulatory proteins, altered metabolism, increased markers of inflammation and impaired immunity. The driving force for muscle wasting in cancer patients is the competition for nutrients between the cancer and the host often complicated by decreased protein/caloric intake. However, the mechanisms that both incite and promote the ongoing process of muscle loss are complex and include factors associated with direct muscle atrophy, including the release of cytokines such as tumor necrosis alpha and interleukin 6, as well as myostatin and activin. One strategy that might ameliorate the cachexia process include therapeutic approaches that block these cytokine mediated pathways and several agents are in development.[4] Another approach has been to try to increase muscle growth signaling through anabolic pathways such as selective androgen receptor modulators (SARM) and ghrelin minetics. A first in class SARM, enobosarm has shown promising results with improvement of muscle mass and physical function in patients with cachexia.[5] Subsequent phase III trials in patients with advanced lung cancer receiving chemotherapy have shown increase in muscle mass in the enobosarm treatment group versus placebo, but physical function testing using stair climb measurement were inconsistent.[6] Meanwhile, trials of anamorelin, a ghrelin receptor agonist have also demonstrated improvement in skeletal muscle mass. In phase III trials in patients with advanced lung cancer and cachexia, improvement in skeletal muscle mass has been seen along with positive effects on improved appetite and weight gain. Again, functional improvement as measured by hand grip strength was not observed.[7] It is not clear why there is a lack of association of these promising agents that increase muscle mass, with functional improvement. This may reflect issues regarding the patient population, the objective test being used, the duration of treatment or other factors. However, these phase III trials in advanced lung cancer represent an important step forward in our understanding of cachexia and possible therapeutic interventions. Currently, as we are moving forward with the development of new agents for cachexia, it is important for us to recognize the magnitude of the problem in our patients. Until CT imaging becomes a standard clinical technique for assessment of muscle mass, we need to rely on our standard clinical approaches of history and physical exam. Perhaps most importantly, is our documentation of the degree of weight loss in our patients as a routine measure at baseline and during treatment just as we assess other patient reported outcomes such as pain, fatigue and functional status. Incorporating weight loss along with body mass index can be a very powerful tool for predicting outcome and survival for our patients.[8] Moreover, it can help us address potential interventions that may be of benefit for them. While current pharmacologic interventions are of limited benefit, exercise and nutritional support are both important interventions for our patients, along with continuing monitoring of appetite, weight and functional performance during treatment.[9] Cancer treatment itself can be associated with an increase in muscle mass, particularly in patients whose tumors respond well to therapy. However, for those patients who progress through therapy, the toxicity of our treatment only compounds the ongoing cachexia process. Better cancer therapeutics combined with optimum supportive care remain the goal of management. 1. Fearon K, Strasser F, Anker SD, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011 May;12(5):489-95. 2. Prado CM, Lieffers JR, McCargar LJ, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncology. 2008; 9(7):629-35. 3. Prado CM, Antoun S, Sawyer MB, Baracos VE. Two faces of drug therapy in cancer: drug-related lean tissue loss and its adverse consequences to survival and toxicity. Curr Opin Clin Nutr Metab Care. 2011;14:250–254. 4 Cohen S, Nathan JA, Goldberg AL. Muscle wasting in disease: molecular mechanisms and promising therapies. Nat Rev Drug Discov. 2015 Jan;14(1):58-74. 5. Dobs AS, Boccia RV, Croot CC, et al. Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. Lancet Oncol. 2013 Apr;14(4):335-45. 6. Crawford J, Prado C, Johnston M, Gralla R, Taylor R, Hancock M, Dalton J. Study design and rationale for the phase 3 clinical development program of enobosarm, a selective androgen receptor modulator, for the prevention and treatment of muscle wasting in cancer patients (POWER Trials). Cur Oncol Rep (2016) 18:37. 7. Temel JS, Currow DC, Fearon K, et al. Phase III trials of anamorelin in patients with advanced non-small cell lung cancer (NSCLC) and cachexia (ROMANA 1 and 2). J Clin Oncol 33, 2015 (suppl; abstr 9500) 8. Martin L, Senesse P, Gioulbasanis I, Antoun S, et al. Diagnostic criteria for the classification of cancer-associated weight loss. J Clin Oncol. 2015 Jan 1;33(1):90-9. 9. Crawford J. Clinical results in cachexia therapeutics. Current Opinion in Clinical Nutrition & Metabolic Care. 19(3):199-204, May 2016.

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      ED06.05 - Surgery for Symptom Relief (ID 6451)

      16:00 - 17:30  |  Author(s): S. Taghavi

      • Abstract
      • Presentation
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      Abstract not provided

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      ED06.06 - Decisions in Case of Intractable Symptoms (ID 6452)

      16:00 - 17:30  |  Author(s): J. Klastersky, B. Michel, I. Libert, A. Georgala, M. Obiols, F. Lewis, D. Lossignol

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      Abstract:
      Case report A 55-year-old lady was diagnosed with small cell lung cancer in late 2008. She had been a long-time cigarette smoker without, any other significant medical history. She was a housewife, deeply religious and dedicated mother to 2 children. As a first treatment for her cancer, she received radiotherapy on the right apex and mediastinum, concomitantly with chemotherapy (cisplatin plus etoposide), early in 2009. Six months later, she presented a very painful right shoulder and chest wall. Chemotherapy was resumed, with some improvement of the pain, but late in 2009, radiotherapy had to be administered to the chest for uncontrolled pain; oral etoposide was given without much benefit. The pain progressively increased and the patient was complaining of increasing shortness of breath. As the tumour was clearly progressing, in 2010, with further lung, bone and liver involvement, a decision was made to discontinue any specific oncological treatment. Both symptoms pain and dyspnea increased in intensity and became uncontrollable late in 2010; the patient and her family requested sedation at any cost. The patient was started on palliative sedation and died peacefully after 2 days; with her family present. Supportive and palliative treatments for pain Table 1 summarizes the time evolution of the patient and the corresponding interventions as far as analgesics and co-analgesics are concerned. Management of dyspnea over the course of her disease, the patient experienced progressive dyspnea which could be managed with oxygen, corticoids, benzodiazepines and bronchodilatating aerosols, as well as physical therapy and hypnosis. Dyspnea became major and beyond control the day prior to the last hospitalization and was a reason for accelerated sedation. Figure 1 Management of depression The patient had multiple reasons for being severely depressed: her mother was experiencing lung cancer at the same time ; the patient was concerned about becoming increasingly a burden for her family; she was aware of her worsening condition and realizing that her life would end soon; she was extremely anxious to have to die in intractable pain. The management of the patient’s depression included the following: monthly consultation with an onco-psychiatrist and weekly visits to a psychologist-social worker ; psychotropic drugs ; several sessions of hypnosis. Palliative sedation That the control of the patient’s pain and/or dyspnea might require palliative sedation has been discussed since 2010 (time of worsening of her symptoms) between the patient, her family and the caregivers. The patient and her family spoke openly about end-of-life issues, always emphasizing not to let the patient die in severe pain. After making the decision to resort to sedation in case of intractable symptoms, the patient and her family expressed a sense of relief that her suffering could and would be alleviated. When the patient expressed unbearable pain and dyspnea, the mobile nursing team started her on midazolam, scopolamine and methadone by sub-cutaneous route, with no clear-cut response; the patient was brought to the hospital, where the same medications were given intravenously, with the addition of haloperidol. No attempt to lift the sedation process (respite sedation) was made, according to the patient’s will. The patient was able to rest comfortably and died peacefully after 2 days, with her family at her side. Discussion In case of dyspnea due to lung cancer progression, corticosteroids, morphine and oxygen are used since many years ; novel options were introduced timidly during the last years. These new options include non-invasive ventilation, high-flow oxygen and rational use of medications usually prohibited in patients with respiratory distress, such as benzodiazepines, antidepressants and synthetic opioids [1]. The World Health Organization (WHO) scale for cancer-related pain proves to be an effective approach to pain management in cancer patients [2], and many variations based on it have been proposed [3]. However, these approaches represent pragmatic and empiric attitudes that are rarely evaluated in prospective studies. There is also a lack of consensus about the use of co-analgesia and other supportive approaches for refractory pain [5]; although pragmatic recommendations exist, a comprehensive algorithm for the management of refractory pain is still lacking. Based on the experience in our supportive care unit, we proposed a comprehensive model for the progressive management of pain in cancer patients (Figure 1). Finally, the approach to pain (or other symptoms) that is beyond medical control, fortunately a relatively rare situation, has not been clearly defined [6;7]. Palliative sedation or euthanasia is always an emotionally and ethically challenging event for all involved and implies to meet the needs of the patient and family but also those of the caregivers [8; 9; 10] and requires repeated and professional counselling with the patient and family as well as regular debriefing sessions with the medical and nursing teams. Although the decision to offer and provide palliative sedation or euthanasia (if requested by the patient and not illegal) is never easy, it should be seen, however, as the medical duty to safeguard the patient’s autonomy, the principle of individual freedom to make choices. Figure 2 References 1. Cabezón-Gutiérrez L, Khosravi-Shahi P, Custodio-Cabello S, Muñiz-González F, del Puerto Cano-Aguirre M, Alonso-Viteri S. Opioids for management of episodic breathlessness or dyspnea in patients with advanced disease. Support Care Cancer 2016;24:4045-55 2. Meuser T, Pietruck C, Radbruch L, Stute P, Lehmann KA, Grond S. Symptoms during cancer pain treatment following WHO-guidelines: a longitudinal follow-up study of symptom prevalence, severity and etiology. Pain 2001; 93:247-57 3. Zech DF, Grond S, Lynch J, Hertel D, Lehmann KA. Validation of World Health Organization Guidelines for cancer pain relief: a 10-year prospective study. Pain 1995; 63:65-76 4. Swarm RA, Abernethy AP, Anghelescu DL, et al. Adult cancer pain. J Natl Compr Canc Netw 2010;8:1046-86 5. Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. A comprehensive review of opioid –induced hyperalgesia. Pain Physician 2011; 14:145-61 6. Council on Scientific Affairs, American Medical Association. Good care of the dying patient. JAMA 1996;275:474-8 7. Field MJ, Cassel CK, eds. Approaching death: improving care at the end of life. Washington DC: : National Academy Press, 1997 8. de Graeff A, Dean M. Palliative sedation therapy in the last weeks of life : a literature review and recommendations for standards. J Palliat Med 2007; 10:67-85 9. Olsen ML, Swetz KM, Mueller PS. Ethical decision-making with end-of-life care: palliative sedation and withholding or withdrawing life-sustaining treatments. Mayo Clinic Proc 2010;85:949-54 10. Lossignol D. End-of-life sedation: is there an alternative? Curr Opin Oncol. 2015;27(4): 358-64





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    ED02 - Palliative Care in Lung Cancer: A Global Challenge (ID 264)

    • Event: WCLC 2016
    • Type: Education Session
    • Track: Palliative Care/Ethics
    • Presentations: 1
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      ED02.05 - Palliative Care in Iran (ID 6431)

      11:00 - 12:30  |  Author(s): R. Malayeri

      • Abstract
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      Abstract:
      It is well known that palliative care is a necessity in cancer patients, as early on as the time of diagnosis. In adult oncology, there is evidence to suggest early specialist palliative care improves HRQOL, mood, treatment decision-making, health-care utilization, advanced care planning, patient satisfaction, and end-of-life care (1). Early admission to community-based palliative care also reduces the use of Emergency departments by cancer patients in the 90 days before death (2). Palliative care for cancer patients is rather new in Iran and has a history of less than 7 years. Here we give an overview on the status of palliative care in Iran. We also present the demographics of our patients in the first and largest palliative care ward in Iran over the last two years. Iran has a population of around 80 million people. In Iran, cancer is known as the third cause of death. Adult morbidity rate of cancer in different regions of Iran is estimated 48-112 cases per million people among the females and 51-144 cases per million people among the males (3). Also, mortality rate related to cancer was about 53500 people in 2014 (4). The majority of cancer patients expire in the intensive care units (ICU), whereas bed occupancy of ICUs is in crises, being about 100% in Iran. For each ICU bed, 4 people are applicants (5). We currently have around 8 active palliative care units for cancer patients and one palliative care ward in Iran, all run by charities. In these palliative care units, we have oncologists, palliative care specialists, pain specialists, psychologists, spiritual care specialists, social workers and dieticians. A total number of 3677 patients, ages between 16 and 94 (Median 61), of whom 3277 (89%) with a similar age distribution had a cancer diagnosis were referred to our palliative care unit in Firoozgar Hospital, which is run by the Ala Charity, in Tehran in the last three years. 1770 female (54%) and 1457 male (46%) advanced cancer patients were referred. A number of 388 (12%) patients had breast cancer, 339 (10%) had hematologic malignancies, 312 (10%) had esophageal or gastric cancer, 311 (10%) had colorectal cancer, 105 (3%) had a cancer of the CNS, 101 (3%) had lymphoma, 93 (3%) had renal cancer, 87 patients (3%) had ovarian cancer, 81 (2%) had lung cancer, 54 patients (2%) had prostate cancer and 50 (2%) had pancreatic cancer. The other 40% of the cancer patients had either less frequent cancers or their exact cancer site was not recorded. In most countries, the gap between death and specific therapies is considered as an indicator of the quality of physician services and more length of time will be a better indicator for physician services, while cancer patients in health system of Iran receive specific treatment and chemotherapy even to moment of death. To consider countless benefits of home care and the patients’ desire to receive services at home, if we can provide the conditions that at least 20% of end stage cancer patients receive home based palliative care, 1000 deaths will occur at home yearly, and 1000 ICU beds will be released for use for other patients with better prognosis for survival (5). For this reason, the Ala charity has also started free of charge home care services in Isfahan and Tehran. Iran, like many other countries, needs many more palliative care units as well as an expansion of home based palliative care services to advanced and very advanced cancer patients. As palliative medicine is not financially lucrative, charities play a major role in setting up, maintaining and expanding these units. References: Salins N, Ramanjulu R, Patra L, Deodhar J, Muckaden MA. Integration of Early Specialist Palliative Care in Cancer Care and Patient Related Outcomes: A Critical Review of Evidence. Indian J Palliat Care. (2016) 22:252-7 McNamara BA, Rosenwax LK, Murray K, Currow DC. Early admission to community-based palliative care reduces use of emergency departments in the ninety days before death. J Palliat Med. (2013) ;16:774-9 Mousavi SM, Gouya MM, Ramazani R, et al. Cancer incidence and mortality in Iran. Annals of Oncology. (2009) ;20:556–63. World Health Organization. Cancer country profiles in Iran 2014. Geneva: WHO; 2014. [cited 29 August 2015]. Avilable from: http://www.who.int/cancer/country-profiles/en/ Heydari H. Home-based Palliative Care: A Strategy for Keeping Intensive Care Unit Beds Vacant. Int J Community Based Nurs Midwifery. (2016);4:186-7.

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