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L. Morgan

Moderator of

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    MS14 - Interface Between Disease Modifying Treatment and Palliation (ID 31)

    • Event: WCLC 2013
    • Type: Mini Symposia
    • Track: Supportive Care
    • Presentations: 4
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      MS14.1 - Sliding Slope Between Cure and Palliation: Local Cure in Disseminated Disease (ID 521)

      14:00 - 15:30  |  Author(s): B. Slotman

      • Abstract
      • Presentation
      • Slides

      Abstract
      For a long time, radiotherapy for lung cancer were considered in terms of being either curative, palliative or radical. Conventional radiotherapy for early stage NSCLC was general considered ‘ curative’, but the more modest expectation in patients with locally advanced NSCLC led to it being referred to as ‘radical’, as disease recurrences was considered very likely. In metastatic NSCLC, the role of radiotherapy was considered only in a palliative context, since it was generally accepted that in disseminated disease, local therapies could never be curative. These classifications have been reappraised in the light of recent data. In small cell lung cancer (SCLC), which has a very high risk of distant spread, recent studies have established that local treatments can extent survival and contribute to cure. This is not only the case for thoracic radiotherapy, but also for prophylactic radiotherapy to the brain (PCI; prophylactic cranial irradiation). Studies in patients with limited disease SCLC have shown a survival benefit of about 5% at 3 years,a benefit of similar magnitude to that for thoracic radiotherapy in this patient group. Even in patients with proven disseminated SCLC (extensive stage), the use of PCI has improved survival. In a randomized trial, patients who received PCI had a 1 year survival of 27% compared to 13% for patients who did not receive PCI [1]. A study on the use of thoracic radiotherapy after the completion of chemotherapy in patients with ES-SCLC has recently been closed and the results are awaited next year. With the advancements in radiotherapy techniques, we can now ablate tumors with very high doses, and with great precision using stereotactic techniques. Local control rates in excess of 90% are obtained and in fit, potentially operable patients, 5-year survival rates above 60 % are achieved [2,3]. These ablative radiation doses may also exert a benefical immunological effect both locally and systemically. The same principles of high-dose high-precision radiotherapy are being applied in patients with a limited number of metastases (oligometastases). This patient group is increasingly being identified due to improved imaging techniques, and interest is growing due to the availability of more effectivity of systemic therapy in subgroups of lung cancer. Aggressive treatment of metastases by surgery or ablative therapy, such as SBRT, might offer a real chance of cure for these patients. We have initiated a clinical study to evaluate the benefit of this approach [4]. References 1. Slotman BJ et al., New Engl J Med 357, 664-72, 2007. 2. Onishi H et al., Int J Radiat Oncol Biol Phys 75, 243-247, 2011. 3. Lagerwaard FJ et al., Int J Radiat Oncol Biol Phys 83, 348-53, 2012 [updated]. 4. Palma D et al., BMC Cancer 12, 305, 2012.

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      MS14.2 - Decision Making; When to Stop Disease Modifying Treatment (ID 522)

      14:00 - 15:30  |  Author(s): C. Manegold

      • Abstract
      • Presentation
      • Slides

      Abstract
      Decision making in advanced NSCLC undoubtedly should primarily consider evidence based treatment standards recommended by international guidelines (1, 2) According to international guidelines, decision making in 2013 is characterized by customizing therapy in advanced non-small cell lung cancer, by selecting a specific therapeutic regimen based on tumor histology and molecular biology. This refers to first-line therapy in patients with good performance status, but also to subsequent lines of therapy since antineoplastic drugs and regimens used in induction therapy directly influence the selection of agents/regimens considered for second/third-line treatment. The availability of antineoplastic monoclonal antibodies, small molecules and newer cytotoxic such as pemetrexed, the antiangiogenic bevacizumab as well as the tyrosine kinase inhibitors erlotinib, gefitinib and crizotinib has recently changed the treatment algorithm of advanced NSCLC. Therapy optimization by modern medical therapy is characterized by treatment individualization based on predictive factors. This process seems to continue since other products holding considerable promise for the near future such as tumor vaccines and other immunotherapeutic approaches, anti-angeniogenic agents, and newer EGFR-targeting monoclonal antibodies have already reached the level of phase III-testing or the registration process. Today’s recommendation can be summarized as follows: First-line therapy: In patients with good performance status with non-squamous tumors haboring an activating EGFR-mutation, an EGFR tyrosine kinase inhibitor may be the leading option, not only because of being active but also because of its feasibility and improved toxicity profile (3-5). In patients with non-squamous cell tumors not expressing EGFR-mutations, combination therapy remains standard with pemetrexed as the preferred partner of cisplatin (6). Furthermore, it has been demonstrated that in non-squamous NSCLC the addition of bevacizumab to standard doublet therapy improves survival (7, 8). With regard to patients with squamous cell tumors gemcitabine, vinorelbine or taxanes in combination with platinum-based agents remain the chemotherapeutic standards. Bevacizumab and pemetrexed are not recommended in squamous cell tumors either because of the agents toxicity profile (bevacizumab) or because of being less effective in this particular histological subtype (pemetrexed). For elderly patients not being fit for standard doublet chemotherapy medical treatment requires modification. Here single agent therapy is widely considered to be the preferred option for maintaining quality of life, reducing tumor association symptoms and improving survival (9). Fit elderly patients benefit from combination chemotherapy as much as younger patients and platinum-based chemotherapy is recommended as well (10, 11). Combination therapy remains investigational in patients with poor performance status (≥ PS 2), and single agent chemotherapy is the preferred option (12). Second-line therapy: In patients with disease progression during or after completion of induction (first-line) chemotherapy second-line therapy is indicated if the patient remains in good clinical condition. Selection of drugs for second-line therapy is based on whether the drug has been used earlier, the toxicity profile or the patients wish. The approved options for second-line therapy are docetaxel and pemetrexed (in case of non-squamous histology), erlotinib and gefitinib (in tumors expressing activating EGFR-mutations) (13-16). Crizotinib has recently been registered for second-line therapy in ALK-positive tumors (17). Maintenance therapy: The prolongation of induction therapy represents an evidence based new option to improve outcome in advanced NSCLC, in general and with strong implications for second line therapy, in particular. Three randomized studies investigated pemetrexed and erlotinib as maintenance therapy following 4 cycles of chemotherapy (18-21). In these trials switch-early second-line- (pemetrexed, erlotinib) or continuation-true- (pemetrexed) maintenance therapy has significantly increased PFS and OS. Based on this given evidence these two compounds have been registered for maintenance therapy in patients with advanced NSCLC, not progressing following 4 cycles of first-line standard platinum-based therapy. According to the European Medicines Agency (EMA) pemetrexed is indicated as monotherapy for maintenance treatment of locally advanced or metastatic NSCLC other than predominantly squamous cell histology in patients who’s disease has not progressed immediately following platinum-based chemotherapy, including platinum-pemetrexed combinations, and erlotinib is indicated as monotherapy for maintenance treatment in patients with locally advanced or metastatic NSCLC with stable disease after 4 cycles of standard platinum-based first-line therapy. When prescribing erlotinib, clinical factors associate with prolonged survival should be taken into account. There is clearly more which must be considered and which would lead to stop or even not to initiate a modern medical therapy. Even if national and international treatment recommendations undoubtedly represent the backbone of the decision making process, the management of patients with advanced non-small cell lung cancer often clinically requires modification for a number of reasons not necessarily considered by guidelines.This refers to first and subsequent-line treatment as well. The majority of lung cancer patients are older patients and often express specific age related treatment expectations. Other relevant factors for decision making in a non-curative setting are patient social environment and patient psychological status, regulations of national health care providers and reimbursement systems, drug availability, diagnostic and health care infrastructure. These circumstances modify decision making and lead to the use of older agents and regimens, to changes in dosing and scheduling of newer agents and regimens, to single agent therapy, to a reduction of treatment cycles and to a more free indication of best supportive care measures. Our increased understanding of the molecular biology of lung cancer and the change of its epidemiology has opened up venues for more rational treatment strategies and at the same time has challenged the additional diagnostic algorithms, the established health care financing and the complex process of drug development. Customized therapy and therapeutic targeting were made possible through the identification of new treatment predictors and the development of a number of antineoplastic agents which have shown clinical evidence for being more beneficial then the treatment standard in selected patients. Consequently, therapy individualization by histology and molecular markers has significantly influence the work of pathologists around the globe and the process of obtaining a therapeutically relevant tumor diagnosis. Not only histological sub-typing becomes clinical relevant but molecular information is also of increasing importance for treatment selection. Routine molecular testing in certified laboratories must be established, and this diagnostic process should ideally performed under the guidance of evidence based recommendation such as the recently published guidelines from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology for the molecular testing to select patients for EGFR-ALK-thyrosine kinase inhibitors (22). This process requires advanced diagnostic techniques and expertise. Investigating and implementing medical targeting in lung cancer because of its large dimension is costly and characterize by the limitation of financial and clinical resources, and currently not every where available. Since the majority of large randomized phase III trials during the last decade turned out negative in their primary endpoints, the time of conducting trials on large unselected patient population seems definitely over and the classical investigational strategy must probably be replaced by smaller trials in selected patients, and trials using study endpoints which can function as substitutes for the traditional overall survival endpoints (23). This inevitable change in the altitude of conducting clinical trials will increase the need for patients treated in clinical trials and, therefore, has a significant impact in decision making in advanced NSCLC. Another hurdle for making promising therapies difficult to be generally prescribed are that clinical evidence of being beneficial and the scientific rational do not necessarily equal clinical practicability and reimbursement in a given cultural and economic system. For Europe and specifically Germany it is important that an agent has reached a positive vote by the registration agency EMA and that it find acceptance by the national health care providers responsible for reimbursement. For this reasons the clinical evidence of being beneficial must be well documented and strong. Information about treatment selection by predictive factors and treatment restriction to patients who benefit the most is very welcome. In addition, if the treatment selection requires advanced diagnostic testing generally accepted and validated methods should easy to be reached and should provide reliable and reproducible results by at the same time being cost effective. References: 1. Azzoli et al, J Clin Oncol 29, 3825-3831, 2011 2. Peters et al, Ann Oncol 23 (suppl. 7), 56-64, 2012 3. Mok et al et al, N Engl J Med 361, 947-957, 2009 4. Zhou et al, Lancet Oncol 12, 735-742, 2011 5. Rosell et al, Lancet Oncol 13, 329-346, 2012 6. Scagliotti et al, J Clin Oncol 26, 3543-3551, 2008 7. Sandler et al, N Engl J Med 355, 2542-2550, 2006 8. Reck et al, J Clin Oncol 27, 1227-1235, 2009 9. Gridell et al, J Natl Cancer Inst 95, 362-372, 2003 10. Langer et al, J Clin Oncol 22 (suppl), 639 (abstr. 2571), 2003 11. Quoix et al, Lancet 378, 1079-1088, 2011 12. Gridelli et al, Ann Oncol 15, 419-426, 2004 13. Shepherd et al, J Clin Oncol 18, 2095-2103, 2000 14. Hanna et al, J Clin Oncol 22, 1589-1597, 2004 15. Thatcher et al, Lancet 366, 1527-1537, 2005 16. Douillard et al, J Clin Oncol 28, 744-752, 2010 17. Shaw et al, N Engl J Med 368, 2385-2394, 2013 18. Capuzzo et al, Lancet Oncol 11, 521-529, 2010 19. Ciuleanu et al, Lancet 374, 1432-1400, 2009 20. Paz-Ares et al, Lancet Oncol 13, 247-255, 2012 21. Paz-Ares et al, J Clin Oncol 31, 2895-2902, 2013 22. Lindeman et al, J Thoracic Oncol 8, 823-859, 2013 23. Pilz and Manegold, Memo 6, 92-97, 2013

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      MS14.3 - End of Life Discussions - Evidence-Based Communication (ID 523)

      14:00 - 15:30  |  Author(s): J. Clayton

      • Abstract
      • Presentation
      • Slides

      Abstract
      Advance care planning refers to a “process of discussion, reflection, understanding and communication between a patient, their family and health providers for the purpose of clarifying values, treatment preferences and goals of end of life care” (1). Advance care planning provides a formal means of ensuring health professionals and family members are aware of the patient’s wishes for care if they were to become too unwell to speak for themselves in the future. This process may include the patient completing an Advance Care Directive, which documents their wishes and/or the appointment of a substitute decision maker. Advance care planning is a patient-centred initiative that promotes shared-decision making and supports substitute decision-making, where appropriate, and aims to achieve good end of life care. The potential benefits of advance care planning for patients with advanced lung cancer have been highlighted in recent literature and clinical practice guidelines (2-4). However, there are many barriers to implementing advance care planning in this setting including patient, family, health professional and system related factors. In particular doctors and nurses caring for patients with lung cancer may be reluctant to raise the topic of advance care planning for fear of upsetting patients or they may lack confidence in knowing how to discuss it. This talk will focus on evidence-based strategies and practical tips for health professionals when having advance care planning discussions with patients with advanced lung cancer and their families. Recommendations from Australian “Clinical practice guidelines for communicating prognosis and end-of-life issues with adults in the advanced stages of a life-limiting illness, and their caregivers” will be described (5). The key recommendations are for health professionals to: Prepare for the discussion, where possible; Relate to the person; Elicit patient/caregiver understanding and information preferences; Provide information, tailored to the individual needs of both patients and their families; Acknowledge emotions and concerns; (foster) Realistic hope; Encourage questions and further discussions; and Document what had been discussed. (PREPARED). Sample phrases and useful questions for facilitating advance care planning discussions will be presented. Further resources regarding advance care planning will be provided (6-9). References: (1) Royal Australasian College of General Practitioners Advance Care Planning Definition http://www.racgp.org.au/your-practice/business/tools/support/acp/ (2) Mack JW, Cronin A, Keating NL et al. Associations between end-of-life discussion characteristics and care received near death: a prospective cohort study. Journal of Clinical Oncology 2012; 35: 4387-4395 (3) (USA) National Comprehensive Cancer Network: Practice guidelines in oncology: Palliative care. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (4) Smith, T, Clayton, J, Michael, N. What is the role of advance care planning and timing of referral for patients with lung cancer? [Version URL: http://wiki.cancer.org.au/australiawiki/index.php?oldid=47787, cited 2013 Aug 26]. Available from http://wiki.cancer.org.au/australia/Clinical_question:What_is_the_role_of_advance_care_planning_and_timing_of_referral_for_patients_with_lung_cancer%3F. In: Cancer Council Australia Lung Cancer Guidelines Working Party. Clinical practice guidelines for the treatment of lung cancer. Sydney: Cancer Council Australia. Available from: http://wiki.cancer.org.au/australia/Guidelines:Lung_cancer (5) Clayton JM, Hancock KM, Butow PN, Tattersall MHN, Currow DC. Clinical practice guidelines for communicating prognosis and end-of-life issues with adults in the advanced stages of a life-limiting illness, and their caregivers. Medical Journal of Australia 2007; 186: S77- 108 https://www.mja.com.au/journal/2007/186/12/clinical-practice-guidelines-communicating-prognosis-and-end-life-issues-adults (6) The conversation project http://theconversationproject.org (7) Respecting Patient Choices http://www.respectingpatientchoices.org.au (8) Oncotalk http://www.oncotalk.info (9) Vital talk http://vitaltalk.blogspot.com.au

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      MS14.4 - Transition to End of Life Care (ID 524)

      14:00 - 15:30  |  Author(s): C.S. Karapetis

      • Abstract
      • Presentation
      • Slides

      Abstract
      Metastatic lung cancer remains an incurable condition despite recent advances in medical therapy. New treatments can prolong survival and enhance quality of life for patients. Lung cancers can shrink and impressive responses may divert attention from the inevitable reality that the cancer will eventually acquire resistance to therapy. In the current era, patients are guided through multiple lines of therapy; first line, maintenance, second-line and so on. Such ‘lines of therapy’ extend the time on active therapeutic measures designed to alter the biological behavior of advanced lung cancer. Cancer centres that conduct clinical trials may offer potential active intervention beyond the proven ‘lines of therapy’, thereby extending time on active therapy. This may delay the transition to end-of-life care, but the likelihood of benefit with therapies beyond 2[nd] line is low. Whilst oncologists have a greater armamentarium in the fight against lung cancer, there comes a time for every patient when the medical advice will be to stop ‘active therapy’ as there is no prospect of benefit. The focus of care will be on symptom control with acceptance of palliative care. This is the time when patients accept that medical intervention will not prolong survival time, cannot alter the growth and spread of the cancer and will not influence the harmful effect of the cancer on the body. The body will fail, and in the process a functional decline will become obvious. This transition to ‘end-of-life’ care is not a clearly defined time point. Complex decision-making and emotional discussions are usually required. Several issues should be taken into account in determining when anti-cancer therapies should continue to be utilised or when such measures should be abandoned. These issues include: The likelihood of a beneficial response to a proposed therapy The safety and toxicity of the proposed intervention The patient’s ‘performance status’ – an overall measure of functional capacity Comorbidity and organ dysfunction Patient preference There are validated measures of prognosis that may assist in determining when this transition to palliative care should commence, including extent of cancer, weight loss, serum albumin, white cell count, neutrophil to lymphocyte ratio, lactate dehydrogenase and measures of critical organ function (cerebral, pulmonary, liver and renal). The synthesis of all of this information, a global assessment of the patient and knowledge of all the available treatment options is required to determine the timing of transition to ‘end-of-life’ care. The transition is usually handled through a multidisciplinary approach, with potential involvement of multiple health care professionals including the general practitioner, palliative care physician, medical oncologist, radiation oncologist and surgeon. Additional input from health care professionals in the fields of psychology, psychiatry, dietetics, social work and physiotherapy can enhance the quality of care in this transition period, depending on the degrees of distress and disability. Expert counseling is required. Involvement of the primary carers and family in discussions and decision-making is also important. Optimising care for patients during the late stages of cancer should focus on alleviating symptoms, allow planning for death, facilitate arrangements and enable personal commitments before death, dealing with grief and supporting the caregivers. These measures can improve quality of life, reduce anxiety and permit a more peaceful death. Ongoing active cancer therapies may introduce adverse events, require additional hospital visits and expose patients to invasive procedures. This can delay the introduction and implementation of optimal palliative care in the ‘end-of life’ period. The transition to end of life care should also be an opportunity to consider advanced directives. This issue needs to be discussed in a sensitive manner. Decisions around intensive medical intervention and confirmation of ‘not-for-resuscitation’ status will allow for patient wishes to be respected and permit patient autonomy at this difficult stage. An appreciation and acceptance of ‘end’-of-life’ care, when the prognosis is clearly very poor and death from an advancing lung cancer inevitable, will improve the prospect of allowing a comfortable death, a ‘good death’. This should be a goal that every cancer specialist seeks for patients with incurable cancer.

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Author of

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    O11 - Symptom Management (ID 137)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Supportive Care
    • Presentations: 1
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      O11.05 - DISCUSSANT (ID 4006)

      16:15 - 17:45  |  Author(s): L. Morgan

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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