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M. Millward
Moderator of
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E06 - Issues in Current Multidisciplinary Practice (ID 6)
- Event: WCLC 2013
- Type: Educational Session
- Track: Combined Modality
- Presentations: 4
- Moderators:L. Gaspar, M. Millward
- Coordinates: 10/28/2013, 14:00 - 15:30, Bayside 204 A+B, Level 2
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E06.1 - Optimal Chemotherapy in Combined Modality Therapy for NSCLC (ID 398)
14:00 - 15:30 | Author(s): E. Vokes
- Abstract
Abstract
Over the last decade, combined modality therapy has been established as standard of care for patients with locoregionally advanced unresectable non-small cell lung cancer (1). Both induction chemotherapy followed by radiation as well as concomitant chemoradiotherapy have been shown to be superior to radiotherapy alone and both approaches extend progression-free and overall survival. In direct comparison, concomitant chemoradiotherapy has been shown to be superior to induction in several randomized phase III trials as well as meta-analyses, likely due to enhanced locoregional control due to the chemotherapy radiation sensitization effect (2, 3). Currently about 20 to 30% of patients can be cured. While there are established clinical prognostic factors, very little information exists to more precisely guide prognosis or therapeutic approach for individual patients. In trying to improve survival outcomes induction chemotherapy was added to concomitant chemoradiotherapy but failed to result in superior outcome compared to concomitant chemoradiotherapy alone.(4). Similarly, consolidation chemotherapy or maintenance therapy with erlotinib in patients unselected for molecular characteristics did not improve survival compared with concomitant chemoradiotherapy alone (5,6). Several chemotherapy regimens have been investigated in the concomitant setting including the mitomycin/vinblastine/cisplatin (MVP) regimen, carboplatin/paclitaxel given weekly (and this regimen has consolidation chemotherapy for two cycles built in) and cisplatin/etoposide. The latter two are frequently used standards in control arms for current randomized trials. There has also been interest in the combination of carboplatin and pemetrexed given the superior single modality activity of the platinum/pemetrexed regimen in non-squamous cell tumors (7). It has been demonstrated that this drug combination can be given at full systemic doses in combination with radiation, thus providing good systemic coverage to eradicate micro-metastases as well as locoregional radiation enhancement. Whether any of these regimens is superior to another is not clear and few direct comparisons have been completed. Japanese investigators compared carboplatin/taxol with carboplatin/irinotecan and the MVP regimen in combination with concomitant radiation and reported equivalent outcomes with these regimens(8). In a small trial comparing carboplatin/taxol with cisplatin/etoposide and radiotherapy, the platinum/etoposide regimen appeared to be superior; however, the number of patients was very limited at approximately 30 per arm (9). Cisplatin/pemetrexed vs. carboplatin/pemetrexed has also been compared in a randomized phase II format supporting a trend for superiority of cisplatin-based therapy as has been shown for other stages of non-small cell lung cancer as well (10). A large randomized phase III trial comparing cisplatin/etoposide with cisplatin/pemetrexed each with concomitant radiotherapy to 66 Gy has been completed. This study was closed after a futility analysis at near completion of planned accrual and a full analysis of this trial is awaited for the future. Targeted therapies have also been of interest. While they have matured to be standard therapy for many patients with stage IV disease their role in earlier stages remains under-investigated. In a number of uncontrolled trial, the addition of erlotinib or gefitinib to radiation therapy with or without additional chemotherapy has been shown to be feasible. In the Alliance Cooperative Group (formerly CALGB), a recent trial looking at induction chemotherapy with carboplatin and albumin-bound paclitaxel followed by erlotinib and concomitant radiotherapy for patients with poor-risk stage III non-small cell lung cancer was completed. Median progression-free and overall survival times of 11 months and 16 months respectively were encouraging. However, no comparative arm of radiotherapy alone was included in the trial design (11). Similarly, cetuximab has been integrated into this treatment approach. RTOG 0324 reported encouraging pilot data from the addition of cetuximab to carboplatin/paclitaxel-based concurrent chemoradiation and consolidation chemotherapy(12). A randomized trial comparing the base regimen vs. the base regimen plus cetuximab in this setting has been completed and mature results are expected in the near future. It should be cautioned however, that the larger clinical experience with the addition of cetuximab to concurrent chemoradiotherapy regimens to date has been disappointing. A randomized phase II study conducted by the CALGB (CALGB#30407) found no obvious clinically significant benefit from the addition of cetuximab to carboplatin/pemetrexed radiotherapy (7). Median survival times were 21.2 and 22.4 months respectively for the two study arms. Similarly, controlled trials investigating the addition of cetuximab in patients with esophageal or head and neck cancer to concomitant chemoradiotherapy have not shown a statistically significant benefit compared to chemoradiotherapy alone. Current research interest is focused on the treatment of patients with molecular abnormalities, in particular EGFR mutations or EML/alk translocation. For these patients, a study investigating induction chemotherapy with either erlotinib or crizotinib, respectively followed by standard concurrent chemoradiation vs concurrent chemoradiation alone is about to be activated. Similarly, immunological approaches are of interest. At present, no data from studies investigating CTLA-4 or PD1 inhibitors are available. However, a randomized trial investigating the BLP25 vaccine, a liposome MUC1-based vaccine, has recently been reported. This vaccine attempts to induce a proliferative T-cell response to the MUC1 antigen which is frequently overexpressed and hyper-glycosylated in non-small cell lung cancer. In this trial, patients completed standard combined modality therapy (either induction or concomitant chemoradiotherapy) and were then randomized to either a placebo or the active vaccine. For the overall study cohort a trend in survival was observed which was more pronounced in a planned subset analysis of patients receiving concomitant chemoradiotherapy (13). This study adds support to further investigations to vaccine-based approaches. While current standard therapy approaches do result in consistent cure rates of 20-30% of patients, further progress will depend on the development of more specific combined modality approaches. Immunological and molecularly driven clinical trials will be of particular interest in this regard. -
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E06.2 - Staging and Early Response Assessment in Combined Modality Therapy for NSCLC (ID 399)
14:00 - 15:30 | Author(s): D. Ball, S. Everitt, T. Kron, S. Siva, M. Macmanus
- Abstract
- Presentation
Abstract
For years radiation oncologists have dreamed of being able to dynamically adapt treatment to the response of normal and tumor tissues observed during a protracted course of radiotherapy. An obvious goal is to adjust the PTV as the GTV shrinks during treatment, which may improve dose volume metrics in the organs at risk, especially lung. Reinflation of atelectatic lung in response to tumour size reduction may require adjustment of PTV size and position to avoid geographic miss. Cone beam CT (CBCT) has revolutionised the ability to regularly image soft tissue, although it is less useful for targets within the mediastinum or those defined primarily by FDG PET. The main limiting step is the time required to develop an adaptive treatment plan without interrupting treatment. Experience suggests that tumor reduction needs to be substantial to have a meaningful impact on the dose volume metrics. The use of serial FDG PET during treatment to detect residual activity and to use this as a surrogate for persistent disease for adaptive radiotherapy is under investigation. This is however based on an unproven assumption that such FDG activity is due to tumor and not inflammation. Tumor motion adds further uncertainty, affecting both SUV and intrafraction location of the residual FDG uptake. CBCT may also detect tumor progression. This seems to be uncommon.(1) When it occurs, apart from discontinuing futile treatment to avoid unnecessary toxicity, can anything else be done? Our group has investigated the use of PET tracers to detect functional changes in tumour during treatment, including FDG and the thymidine based tracer FLT which we hypothesise images tumour proliferation. Preliminary results indicate that FLT detects functional changes in the tumour earlier than FDG, but the clinical implications of this are unknown.(2) One patient with clinical progression had increased uptake of FLT detected at 20 Gy, suggesting accelerated repopulation. The rate of treatment was accelerated with twice daily fractionation, resulting in a reduction in FLT uptake, providing anecdotal proof of principle. Accelerated repopulation has also been indirectly observed with induction chemotherapy.(3) Imaging with FLT may present an opportunity to detect altered proliferation pre-radiotherapy which may benefit from accelerated fractionation.(4) A further change that may occur during fractionated treatment is reoxygenation. We have observed changes in uptake of the hypoxia PET tracer FAZA during a course of radiotherapy,(5) indicating that hypoxia is present in some tumors pre-treatment, although surprisingly little use is made of this knowledge in clinical practice. Changes observed in normal tissue response may also present opportunities for adaptive treatment. The patient can be used as a biological dosemeter, and the occasional patient will require truncation of treatment because of esophagitis. Is this increased sensitivity a surrogate for inherently increased radiosensitivity within the tumor, indicating that a higher tumor dose is unnecessary for such patients? Our group has observed changes in normal lung during treatment using ventilation/perfusion imaging, opening up prospects of avoiding functioning (as opposed to anatomical) lung with beam redirection.(6) Conclusions: A number of tools are now available to detect tumor and normal tissue response to radiotherapy during treatment. These changes may be anatomic or functional, including changes in tumor kinetics or the micro-environment. The challenge now is to turn these observations into clinically useful patient benefits. References 1. Lim G, Bezjak A, Higgins J, Moseley D, Hope AJ, Sun A, et al. Tumor regression and positional changes in non-small cell lung cancer during radical radiotherapy. J Thorac Oncol. 2011;6:531-6. 2. Ball D, Everitt S, Hicks R, Callahan J, Plumridge N, Collins M, et al. Differential Uptake of F18-fluoro-deoxy-glucose (FDG) and F18-fluoro-deoxy-l-thymidine (FLT) Detected by Serial PET/CT Imaging During Radical Chemoradiation for Non-Small Cell Lung Cancer (NSCLC). . J Thorac Oncol 2012;7:S238. 3. El Sharouni SY, Kal HB, Battermann JJ. Accelerated regrowth of non-small-cell lung tumours after induction chemotherapy. Br J Cancer. 2003;89:2184-9. 4. Baumann M, Herrmann T, Koch R, Matthiessen W, Appold S, Wahlers B, et al. Final results of the randomized phase III CHARTWEL-trial (ARO 97-1) comparing hyperfractionated-accelerated versus conventionally fractionated radiotherapy in non-small cell lung cancer (NSCLC). Radiother Oncol. 2011;100:76-85. 5. Trinkaus ME, Blum R, Rischin D, Callahan J, Bressel M, Segard T, et al. Imaging of hypoxia with (18) F-FAZA PET in patients with locally advanced non-small cell lung cancer treated with definitive chemoradiotherapy. J Med Imaging Radiat Oncol. 2013;57:475-81. 6. Siva S, Callahan J, Hofman MS, Eu P, Martin O, Pope K, Ball D, MacManus M, Kron T, Hicks RJ. Technical considerations and preliminary experience of a pilot study of Gallium-68 VQ 4D-PET/CT in lung radiotherapy. J Thorac Oncol 2012;7: S1182.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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E06.3 - Management of NSCLC Involving the Chest Wall (ID 400)
14:00 - 15:30 | Author(s): D.H. Grunenwald
- Abstract
- Presentation
Abstract
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E06.4 - Treating the 'Borderline' Patient (Moderate PS, Large Tumour, etc.) (ID 401)
14:00 - 15:30 | Author(s): L. Gaspar
- Abstract
- Presentation
Abstract
There is no general agreement on the definition of the “borderline” patient with stage III non-small cell lung cancer (NSCLC). Patients judged to be unsuitable for standard treatment could be of advanced age, unable to undergo cisplatin-based chemotherapy, poor performance status, poor pulmonary function and/or bulky tumors requiring large radiation fields. Since the combination of chemotherapy and radiation therapy (RT) has been adopted as the standard of care, there has been an increased portion of elderly patients who receive it. [1]. Cooperative group studies have demonstrated that the elderly have more toxicity then their younger counterparts and that age is a negative prognostic factor for survival. [2, 3, 4] However, the elderly with good PF still have improved survival with combined chemoRT as opposed to radiation only. Prospective studies in the “borderline” patient by cooperative groups in North America and Asia have had various eligibility criteria. [5, 6, 7, 8]. Those studies accrued slowly or poorly, perhaps due to the 6-7 week RT required in most studies. One RTOG study combining celecoxib and RT did allow either 60 Gy in 6 weeks or 45 Gy in 3 weeks but few patients were treated with the short course. [8] A short of course of RT may be more acceptable to patients who are elderly or have a poor performance status. A retrospective study of patients who did not receive concurrent chemoRT showed that similar survival was seen in patients treated with 45 Gy in 3 weeks as in patients treated with >60 Gy in 6 weeks. [9] Few prospective studies have been done in patients with poor pulmonary function. A retrospective study found that pre-treatment FEV1 was not statistically correlated with symptomatic lung toxicity following concurrent chemoradiation.[10] However, the combination of poor FEV1, advanced age and high mean lung dose correlated positively with pulmonary toxicity. Prospective studies are also lacking in patients with bulky disease for whom large radiation fields are required. Retrospective studies suggest that bulky disease is associated with a higher risk for the early development of metastases and death. [11] Future efforts to improve the therapeutic ratio for borderline patients likely involve the improved ability to predict both benefit and risk for an individual patient. Studies are ongoing using molecular methods to better predict distant metastases-free survival and pulmonary toxicity. [12, 13] 1. van der Drift MA, Karim-Kos HE, Siesling S, et al. Progress in standard of care therapy and modest survival benefits in the treatment of non-small cell lung cancer patients in the Netherlands in the last 20 years. J Thorac Oncol. 2012;7(2):291-8. 2. Schild SE, Mandrekar SJ, Jatoi A, et al. The value of combined-modality therapy in elderly patients with stage III non-small cell lung cancer. Cancer. 2007;110(2):363-8. 3. Langer CJ, Manola J, Bernardo P, et al. Cisplatin-based therapy for elderly patients with advanced non-small-cell lung cancer: implications of Eastern Cooperative Oncology Group 5592, a randomized trial. J Natl Cancer Inst. 2002;94(3):173-81. 4. Non-small cell lung cancer collaborative group. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individuals patients from 52 randomized clinical trials.. BMJ. 7;311(7010) 1995: 8099-909. 5. Lau DH, Crowley JJ, Gandara DR, et al. Southwest Oncology Group phase II trial of concurrent carboplatin, etoposide, and radiation for poor-risk stage III non-small-cell lung cancer. J Clin Oncol. 1998;16(9):3078-81. 6. Atagi S, Kawahara M, Tamura T, et al. Standard thoracic radiotherapy with or without concurrent daily low-dose carboplatin in elderly patients with locally advanced non-small cell lung cancer: a phase III trial of the Japan Clinical Oncology Group (JCOG9812). Jpn J Clin Oncol. 2005;35(4):195-201. 7. Jatoi A, Schild SE, Foster N, et al. A phase II study of cetuximab and radiation in elderly and/or poor performance status patients with locally advanced non-small-cell lung cancer (N0422). Ann Oncol. 2010;21(10):2040-4. 8. Gore E, Bae K, Langer C, et al. Phase I/II trial of a COX-2 inhibitor with limited field radiation for intermediate prognosis patients who have locally advanced non-small-cell lung cancer: radiation therapy oncology group 0213. Clin Lung Cancer. 2011;12(2):125-30. 9. Amini A, Lin SH, Wei C, et al. Accelerated hypofractionated radiation therapy compared to conventionally fractionated radiation therapy for the treatment of inoperable non-small cell lung cancer. Radiat Oncol. 2012;7:33. 10. Wang J, Cao J, Yuan S, et al. Poor baseline pulmonary function may not increase the risk of radiation-induced lung toxicity. Int J Radiat Oncol Biol Phys. 2013;85(3):798-804. 11. Wiersma TG, Dahele M, Verbakel WF, et al. Concurrent chemoradiotherapy for large-volume locally-advanced non-small cell lung cancer. Lung Cancer. 2013;80(1):62-7. 12. Yuan X, Wei Q, Komaki R,et al. TGFβ1 Polymorphisms Predict Distant Metastasis-Free Survival in Patients with Inoperable Non-Small-Cell Lung Cancer after Definitive Radiotherapy. PLoS One. 2013;8(6):e65659. 13. Yin M, Liao Z, Yuan X, et al. Polymorphisms of the vascular endothelial growth factor gene and severe radiation pneumonitis in non-small cell lung cancer patients treated with definitive radiotherapy. Cancer Sci. 2012;103(5):945-50.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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E11 - Practical Aspects of Targeted Therapies (ID 11)
- Event: WCLC 2013
- Type: Educational Session
- Track: Medical Oncology
- Presentations: 5
- Moderators:M. Millward, L. Paz-Ares
- Coordinates: 10/30/2013, 14:00 - 15:30, Plenary Hall, Ground Level
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E11.1 - Who Should We Test for Genetic Alterations, When and How? (ID 422)
14:00 - 15:30 | Author(s): R. Stahel
- Abstract
Abstract not provided
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E11.2 - Management Options at First Progression of EGFR Mutant Tumours (ID 423)
14:00 - 15:30 | Author(s): K. Park
- Abstract
- Presentation
Abstract
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E11.3 - Panel Discussion: MDT - Managing Toxicities and Evaluating Drug Interactions (ID 424)
14:00 - 15:30 | Author(s): P. Yang
- Abstract
- Presentation
Abstract
Managing Toxicities of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-small-cell Lung Cancer Treatment: Focus on Skin and Liver Toxicities Pan-Chyr Yang MD, PhD. Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan. Several recent prospective randomized controlled studies have confirmed the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), including Gefitinib, Erlotinib and Afatinib, in the treatment of non-small-cell lung cancer (NSCLC) harboring EGFR activating mutations (such as L858R or deletions in exon 19). Due to less systematic toxicity, treatment with EGFR TKIs is better tolerated, compared to platinum-based chemotherapy. However, signaling pathways downstream to EGFR are also important to the integrity and function of normal epithelium, and specific adverse effects thus can develop during EGFR TKI treatment. Acneiform rash and diarrhea are the most common adverse effects reported in the clinical trials. Although most adverse effects of EGFR TKIs can be well managed without treatment discontinuation, some uncommon adverse effects, such as hepatotoxicity and interstitial pneumonitis, can be serious and life threatening. Therefore, cautious monitoring for adverse effects is important to NSCLC patients receiving EGFR TKI treatment. Management of Skin Toxicity Various cutaneous adverse effects can occur during EGFR TKI treatment, including acneiform rash, dry skin (xerosis), pruritus, nail or periungual alternations, and hair changes. Acneiform rash usually involves the upper torso, and appears within 2 weeks of treatment initiation. Topical steroids (such as 2.5% hydrocortisone acetate cream), tacrolimus, or antibiotics (such as clindamycin 1% to 2%) are effective treatments for patients with mild acneiform rash. Oral doxycycline (100 mg twice daily) or minocycline (100 mg twice daily) can be used for those with moderate to severe eruptions. When purulent discharge or painful eruptions occurs, secondary infection should be suspected. Broad-spectrum empirical antibiotics are recommended for initial treatment of bacterial super-infection, and appropriate skin swab for culture is required for identification of the causative bacteria. For patients with pruritus during treatment with EGFR TKIs, topical steroid with moderate strength or anti-pruritics (such as 5% doxepin cream) can be used for symptomatic relief. Oral antihistamines may be required for those with more severe symptoms. Topical moisturizing cream or ointment and 12% ammonium lactate cream can help relieving xerosis associated with EGFR TKI treatment. For patients with paronychia associated with EGFR TKI treatment, topical antibiotics and ultrapotent steroids are recommended, and topical silver nitrate application can be used for more severe cases. Although cutaneous toxicities are frequent during EGFR TKI treatment, most of these cutaneous toxicities are mild to moderate in severity, and can be adequately treated without dose reduction or treatment discontinuation. Management of Liver Toxicity Hepatoxicity associated with EGFR TKIs is less commonly reported in clinical trials. However, recent two phase III Japanese clinical trials reported that severe hepatotoxicity (defined as serum hepatic aminotrasferase levels above five times the upper limit of normal) developed in 16% to 28% of patients receiving gefitinib treatment. Furthermore, patients with lethal hepatotoxicity associated with Erlotinib treatment were also reported. Therefore, it is important to regularly monitor serum levels of hepatic aminotransferases in NSCLC patients receiving EGFR TKI treatment. Once severe hepatitis develops during EGFR TKI treatment, timely discontinuation of EGFR TKIs is required, with thorough evaluation of other potential etiologies, such as acute viral hepatitis. It is not recommended to re-challenge the patients with the same EGFR TKIs, which may induce more severe hepatic damage even after dose reduction. The efficacy of steroids in preventing hepatotoxicity is unknown and is not consistent in different reports. Routine steroid treatment is thus not suggested in patients with hepatotoxicity associated with EGFR TKIs. Successful Erlotinib or Gefitinib treatment has been reported in some patients recovering from severe Gefitinib- or Erlottinib-associated hepatotoxicity, respectively. Since different CYP450 enzymes are involved in the metabolism of different EGFR TKIs, trials of different EGFR TKIs may be considered after recovery from hepatitis, especially in responders to EGFR TKI treatment. References: 1. Hirsh V. Managing treatment-related adverse events associated with egfr tyrosine kinase inhibitors in advanced non-small-cell lung cancer. Curr Oncol 2011;18:126-138. 2. Lacouture ME. Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer 2006; 6: 803-12. 3. Wang SH, Yang CH, Chiu HC, Hu FC, Chan CC, Liao YH, Chen HC, Chu CY. Skin manifestations of gefitinib and the association with survival of advanced non-small cell lung cancer in Taiwan. Dermatologica Sinica 2011; 29: 13-18. 4. Lacouture ME, Schadendorf D, Chu CY, Uttenreuther-Fischer M, Stammberger U, O’Brien D, Hauschild A. Dermatologic adverse events associated with afatinib: an oral ErbB family blocker. Expert Rev Anticancer Ther 2013; 13: 721-8. 5. Navarro VJ, Senior JR. Drug-related hepatotoxicity. N Engl J Med 2006;354:731-739. 6. Takeda M, Okamoto I, Tsurutani J, Oiso N, Kawada A, Nakagawa K. Clinical impact of switching to a second EGFR-TKI after a severe AE related to a first EGFR-TKI in EGFR-mutated NSCLC. Japanese journal of clinical oncology 2012;42:528-533.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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E11.3 - Panel Discussion: MDT - Managing Toxicities and Evaluating Drug Interactions (ID 425)
14:00 - 15:30 | Author(s): K. O'Byrne
- Abstract
- Presentation
Abstract not provided
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E11.3 - Panel Discussion: MDT - Managing Toxicities and Evaluating Drug Interactions (ID 426)
14:00 - 15:30 | Author(s): A. Fraser
- Abstract
- Presentation
Abstract
MANAGING TARGETED THERAPY PATIENTS IN A NURSE LED CLINIC Numbers of lung cancer patients on targeted therapies are growing as testing becomes more widely available and cost effective. Lung cancer Clinical Nurse Specialists and Nurse Practitioners are in an ideal position to manage these patients for a number of reasons. Patients on Targeted Therapies present with unique toxicity profiles which CNS’s and NP’s are developing a growing level of expertise in managing. Toxicity profiles include rash, nausea, fatigue, cachexia, diarrhoea, deranged liver function tests, and shortness of breath. Nurses tend to be the most frequently contacted person between clinic visits, triaging and managing toxicities. They are ideally placed to proactively monitor patients, aiding continuity of care and reducing hospital admissions. Patients report improved communication, education around management, and continuity, with reduced treatment related anxiety, in nurse led clinics. Many CNS and NPs can provide a prescription service adding to continuity of care. Support for nurse led clinics is essential to ensure patient safety and should be run alongside the oncologist’s clinics. Competency of the nurse leading the clinic must be maintained through identified supervisors. Utilisation of evidence based tools help to ensure best practice is maintained.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
Author of
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MO13 - SCLC I (ID 118)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:C.K. Liam, E.S. Santos
- Coordinates: 10/29/2013, 10:30 - 12:00, Bayside 201 - 203, Level 2
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MO13.05 - DISCUSSANT (ID 3962)
10:30 - 12:00 | Author(s): M. Millward
- Abstract
- Presentation
Abstract not provided
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P1.12 - Poster Session 1 - NSCLC Early Stage (ID 203)
- Event: WCLC 2013
- Type: Poster Session
- Track: Medical Oncology
- Presentations: 2
- Moderators:
- Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P1.12-010 - Lung cancer clinicians' preferences for adjuvant chemotherapy (ACT) in non-small-cell lung cancer (NSCLC): what makes it worthwhile? (ID 1498)
09:30 - 16:30 | Author(s): M. Millward
- Abstract
Background
Clinicians play an important role helping patients make decisions about ACT, but their views about trade-offs between the benefits and harms of ACT may differ from those of their patients. We sought to determine the minimum survival benefits that lung cancer clinicians judged sufficient to make ACT in NSCLC worthwhile, the factors associated with these judgements, and comparisons with the preferences of their patients.Methods
82 lung cancer clinicians (medical oncologists & thoracic surgeons) completed a self-administered questionnaire. The time trade-off method was used to determine the minimum survival benefits judged sufficient to make ACT worthwhile in 4 hypothetical scenarios. Baseline survival times were 3 years and 5 years and baseline survival rates (at 5 years) were 50% and 65%. Patients’ preferences were those of 122 patients considering ACT for NSCLC elicited in a related study using similar methods. Differences between groups were assessed by 2-sample non-parametric tests. Determinants of preferences were assessed by univariable comparison after normal score transformation. Variance was assessed with the Ansari-Bradley rank test.Results
Most clinicians were male (75%) with a median age of 43 years (range 28-65), had 5 or more years of professional experience (69%), were married (92%), and had dependent children (72%). More were medical oncologists (63%) than thoracic surgeons (31%). The median benefit judged sufficient (by 50% of clinicians) was an extra 9 months (IQR 6-12 months) beyond survival times of both 3 years and 5 years, and an extra 5% (IQR 5-10%) beyond 5-year survival rates of both 50% and 65%. Medical oncologists, compared with thoracic surgeons, judged smaller benefits sufficient to make ACT worthwhile (median benefit 8 months v 12 months, p=0.03). Clinicians’ preferences, compared with patients’ preferences, had the same median benefit (9 months survival time, 5% survival rate) but varied over a smaller range (IQR, 6-12 months v 1-12 months, p<0.001; 5%-10% v 0.1-10% p<0.001).Conclusion
Lung cancer clinicians judged moderate survival benefits sufficient to make ACT in NSCLC worthwhile, but preferences differed according to specialty. Clinicians’ preferences were similar to patients’ preferences, but varied less. Lung cancer clinicians should be mindful of their own preferences and how they may influence discussions and decisions about ACT in NSCLC. -
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P1.12-011 - Patients' preferences for adjuvant chemotherapy (ACT) in early non-small cell lung cancer (NSCLC): What makes it worthwhile? (ID 1773)
09:30 - 16:30 | Author(s): M. Millward
- Abstract
Background
ACT for NSCLC improves overall survival, but the benefits are modest and must be weighed against the harms and inconvenience of the treatment. The aim of this study was to determine the survival benefits judged necessary to make ACT worthwhile for patients with resected early NSCLC, and the factors associated with their judgments.Methods
122 patients considering ACT completed a self-administered questionnaire at baseline (before ACT, if they were having it) and 6 months later (after ACT, if they had it). The time trade-off method was used to determine the minimum survival benefits judged sufficient to make ACT worthwhile in 4 hypothetical scenarios. Baseline survival times were 3 and 5 years and baseline survival rates (at 5 years) were 50% and 65%. All tests were 2-sided and non-parametric. Determinants of preferences were assessed by (rank test) comparison of preferences in groups defined by each factor.Results
Most patients were male (57%) with a median age of 63 years (range, 43-79 years), married (72%) and previous smokers (81%). The majority had had a lobectomy (84%), adenocarcinoma histology (60%), and half had stage II disease (50%). 106 patients decided to have ACT (87%), 16 declined ACT (13%); female sex and age over 65 years were associated with declining. ACT was most commonly 4 cycles (68%) of cisplatin/ vinorelbine (73%). At baseline, the median benefit judged sufficient (by 50% of patients) was 9 months (IQR 1-12 months) beyond life expectancies of 3 years and 5 years, and 5% (IQR 0.1-10%) beyond 5-year survival rates of 50% and 65%. Preferences varied across the entire range of possible benefits (from 0 days and 0% to an extra 15 years and 50%). At baseline, deciding to have ACT (p=0.01) was the only factor that predicted judging smaller benefits sufficient to make ACT worthwhile. At 6 months (n=91), the median benefits judged sufficient were the same as at baseline (9 months & 5%), but preferences varied over a greater range (IQR’s 0-18 months & 0-15%). At 6 months, deciding to have ACT (p=0.02) and better physical (p=0.02), emotional (p=0.004), and overall well-being (p=0.004) during adjuvant chemotherapy were associated with judging smaller benefits sufficient to make ACT worthwhile. Fatigue, nausea, sleeplessness and reduced appetite were the side effects of ACT that patients were most concerned about experiencing (at baseline) and were rated the most troublesome (at 6 months).Conclusion
Most patients judged moderate survival benefits sufficient to make ACT worthwhile, but preferences varied widely and were not predicted by baseline characteristics. Preferences were stable over time. Patients with NSCLC judged larger benefits necessary for ACT than patients with breast and colon cancer in our previous studies. Clinicians should elicit the preferences of individual patients when discussing and making decisions about ACT.
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P2.10 - Poster Session 2 - Chemotherapy (ID 207)
- Event: WCLC 2013
- Type: Poster Session
- Track: Medical Oncology
- Presentations: 2
- Moderators:
- Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level
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P2.10-040 - Prognostic significance, accuracy and usefulness of oncologists' estimates of survival time for patients starting first-line chemotherapy for advanced non-small-cell lung cancer (ANSCLC) (ID 2560)
09:30 - 16:30 | Author(s): M. Millward
- Abstract
Background
Oncologists are frequently required to provide estimates of survival time for their patients with advanced cancer. The aims of this study were to determine the accuracy and prognostic significance of oncologists’ estimates of survival time above and beyond conventional prognostic factors.Methods
Medical oncologists from 26 sites in Australia and New Zealand recorded the “expected survival time in months” for individual patients with ANSCLC prior to randomisation in a trial of first-line chemotherapy with a platinum-based doublet. Blood samples, demographics, tumour and treatment characteristics were collected at baseline along with the oncologist’s rating of each patient using Spitzer’s Quality of Life Index (SQLI). Based on previous studies, we deemed estimates within 0.75-1.33 times observed survival as precise, and expected 50% of patients to live longer (or shorter) than their oncologist’s estimate, 50% to live from half to double their oncologist’s estimate (typical scenario); 5-10% to live ≤¼ of their estimate (worst-case scenario); and, 5-10% to live ≥3 times their estimate (best-case scenario). Associations between estimated and observed survival times in months were assessed with Cox proportional hazards regression before and after adjustment for baseline prognostic factors including age, gender, Eastern Cooperative Oncology Group performance status (ECOG PS), cancer extent, histology, co-morbidities, laboratory results and SQLI.Results
Estimates of survival were available for 244 (98%) of the first 250 patients randomised. Patient characteristics were: median age 64 years; female 40%; adenocarcinoma 64%; ECOG PS 0-1 92%; and distant metastases 71%. After a median follow-up of 21 months there were 172 deaths (69%). The median (interquartile range, IQR) for observed survival was 10 months (5-20) and for estimated survival was 11 months (9-12). Oncologists’ estimates were imprecise (22% from 0.75-1.33 times observed) but well calibrated (47% of patients lived shorter than expected and 53% lived longer than expected). The proportions of patients with observed survival times falling within ranges bounded by simple multiples of their estimated survival times corresponded closely with our a-priori hypotheses: 10% lived ≤1/4 of their estimated survival time, 53% lived from half to double their estimated survival time, and 13% lived ≥3 times their estimated survival time. The oncologist’s estimate of survival time at baseline was the strongest predictor of observed survival in both univariable analysis (HR 0.90, 95% CI 0.86-0.95, p<0.001) and multivariable analysis (HR 0.90, 95% CI 0.86-0.95, p<0.001) accounting for all other independently significant predictors, namely: estimated neutrophil-lymphocyte ratio >5 (HR 3.15, 95% CI 1.76-5.64, p<0.001); haemoglobin <120g/L (HR 1.93, 95% CI 1.3-2.9, p=0.001) and total white cell count >11x10[9]/L (HR 1.55, 95% CI 1.05-2.27, p=0.03).Conclusion
Oncologists' estimates of survival time were independently associated with observed survival time and provided a reasonable basis for estimating worst-case, typical and best-case scenarios for survival. Oncologists’ estimates provide useful additional prognostic information, above and beyond that provided by established prognostic factors. -
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P2.10-041 - Optimising regulatory T cell (Treg) depletion in combination with chemotherapy for enhanced anti-tumour immunity (ID 2576)
09:30 - 16:30 | Author(s): M. Millward
- Abstract
Background
Cytotoxic chemotherapy is widely used to palliate malignant pleural mesothelioma (MM) and non small cell lung cancer (NSCLC). While originally considered detrimental to the immune system, there is now abundant preclinical data showing that chemotherapy can enhance anti-cancer immunotherapy. Tregs are immunosuppressive CD4[+] T cells thought to inhibit anti-tumour immune responses; murine data suggests that Treg eradication may augment existing anti-tumour immunity. Cyclophosphamide (CTX) is immunostimulatory and at low doses selectively depletes Tregs in mice and humans. The primary objective of this study is to identify an optimum dose and schedule of iterative low dose oral CTX for Treg depletion in the context of pemetrexed-based chemotherapy, and to determine how treatment affects the function and phenotype of the cellular immune response.Methods
In this single centre phase 1b study we investigate an optimum dose and schedule of iterative low dose oral CTX for Treg depletion, in the context of pemetrexed-based chemotherapy, and how treatment affects the function and phenotype of the cellular immune response. Thirty-one patients with advanced malignant pleural mesothelioma (MM) or non-small cell lung cancer (NSCLC) received standard doses of pemetrexed ± cisplatin or carboplatin on a 21 day schedule (6 cycles max.). From the second cycle, escalating doses of oral CTX were administered, initially with 50 mg daily. Weekly peripheral blood samples were collected, and the proportion of Tregs within the CD4[+] population (Treg%) determined by flow cytometry, amongst other immunological parameters.Results
31 participants enrolled on the study (27 MM, 4 NSCLC). The mean number of treatment cycles completed was 4.2 from a potential total of 6 cycles, with 20 participants on-study for at least 4 cycles, and the combination was safe and feasible. Contrary to our initial hypothesis, CTX treatment did not reduce the Treg proportion of CD4[+] T cells in peripheral blood, with baseline Treg (CD127[lo]CD25[+]Foxp3[+]) proportion of CD4+ T cells at 4.44±1.56% and no significant change observed when comparing values from the end of each treatment cycle. Doses above 50/100 mg did not improve depletion. However, analysis of the T-effector cell population has demonstrated an increased frequency of CD38[hi]HLA-DR[hi] cells within the total CD8[+] T cell pool. From the perspective of biological relevance, the ratio of activated T-effector cells to Tregs changes minimally during the first cycle of standard care chemotherapy (baseline = 0.21±0.15 T-effectors per Treg); however, from mid-way through cycle 2 (when CTX treatment begins) onward a notable and variable increase in the proportion of activated T-effector cells is observed (end of cycle 3 = 2.21±3.83 T-effectors per Treg). Detailed immunological data will be presented.Conclusion
These data suggests that CTX with chemotherapy can increase the proportion of activated T-effector cells, an observation that has the potential to improve anti-tumour immunity or chemo-immunotherapy efficacy. We postulate that CTX may affect the function rather than numbers of Treg cells, decreasing their ability to suppress the proliferation of CD8+ effector T cells.
