Geriatrics for the Oncologist is guest edited by Stuart Lichtman, MD, FACP, FASCO, and developed in collaboration with the International Society of Geriatric Oncology (SIOG). Visit SIOG.org for more on geriatric oncology.
The Task Forces of the International Society of Geriatric Oncology (SIOG) are active in various fields of geriatric oncology and have produced position papers, consensus statements, and clinical practice guidelines on issues related to cancer in the elderly, which guide clinicians regarding the optimal management of older patients and important age-related considerations. Until recently, older patients were underrepresented in clinical trials, so optimal therapeutic approaches for these patients were generally extrapolated from those for younger patients. The underlying theme or common thread in many of the guidelines, summarized here, is the need for a more objective baseline assessment of older cancer patients to estimate physiologic reserve. It is important to note that the summaries below represent the expert views provided by the respective Task Forces of multidisciplinary expert panels, who developed evidence-based recommendations through a systematic review of the current literature. Further details may be found in the individual publications, as cited. The last three guidelines mentioned in this report, related to taxanes, radiopharmaceuticals in prostate cancer, and chronic lymphocytic leukemia (CLL), and are currently in press.
Comprehensive Geriatric Assessment (CGA)
In 2014, SIOG composed a panel with expertise in geriatric oncology to develop consensus statements of key evidence on the role of geriatric assessment in oncology. The panel concluded that there are mounting data regarding the utility of geriatric assessment in oncology practice; however, additional research is needed to continue to strengthen the evidence base.
The main findings demonstrating the value of geriatric assessment in oncology practice include the following benefits: detection of impairment not identified on routine history or physical examination, ability to predict severe treatment-related toxicity, ability to predict survival in a variety of tumors and treatment settings, and ability to influence treatment choice and intensity.
The panel recommended that the following domains be evaluated as part of a geriatric assessment: functional status, comorbidity, cognition, mental health status, fatigue, social status and support, nutrition, and presence of geriatric syndromes. Several combinations of tools and various models are available for implementation of geriatric assessment in oncology practice.1
Prostate Cancer
In 2013, SIOG updated previous guidelines, including recommendations on assessing individual health status based on physiologic age, rather than chronologic age. On the basis of a validated rapid health status screening instrument (based on the G8 questionnaire [cutoff of < 14] screening score) and simple geriatric assessment, the Task Force recommends that patients be classed into three groups for treatment: (1) healthy or fit patients, who should have the same treatment options as younger patients; (2) vulnerable patients with reversible impairment, who should receive standard treatment after medical intervention; and (3) frail patients with nonreversible impairment, who should receive adapted treatment. This guideline provides recommendations for all treatment modalities.2 [These guidelines are dedicated to the memory of our dear friend Prof. John M. Fitzpatrick, who died on May 14, 2014.]
Radiation Oncology
Radiotherapy is a key component of the management of older cancer patients. The following radiotherapy-specific adaptations/recommendations for various cancer sites may be suitable for older patients.3 It should be noted that the literature to date related to CGA and toxicity in radiotherapy is scant, and this should be addressed in future studies in radiation oncology.
- Fit older patients are candidates for postoperative whole-breast radiotherapy after breast-conserving surgery for invasive cancer and higher-risk ductal carcinoma in situ, although it may be acknowledged that the absolute risk of locoregional or distant recurrence is lower in women over the age of 70, compared to younger patients. Shorter courses of hypofractionated whole-breast radiotherapy have proved to be both safe and effective in certain categories of patients, offering greater convenience, and similar local control. Partial breast irradiation should be considered investigational, as there is insufficient evidence to support it in the elderly. In relation to comorbidities, three-dimensional computed tomography (CT)-based planning is advised to minimize cardiac and lung irradiation, in conjunction with appropriate positioning and immobilization.
- Stereotactic body radiation therapy, which delivers higher-than-conventional doses to small-target volumes in much fewer treatments, is transforming the management of non–small cell lung cancer (NSCLC) in older patients, particularly those for whom comorbidities preclude the use of radical surgery. For inoperable locoregionally advanced NSCLC, concomitant chemoradiation is appropriate in fit elderly patients.
- From a treatment planning viewpoint, adaptive radiation therapy (ART) uses a feedback process for dynamic treatment planning with each fraction. Treatment plans are re-optimized to account for daily variations in physical setup and in internal tumor and normal tissue location and biologic changes. ART may be particularly useful for older patients whose treatment set-up varies due to impaired mobility or unpredictable internal organ motion. Likewise, techniques limiting respiratory motion include controlled breath-hold and abdominal compression, which, while effective, are frequently not tolerated by the elderly. Incorporation of four-dimensional planning CT scans permits better integration of tumour and normal tissue respiratory motion as well as other predictable motion captured during scanning into treatment planning.
- Modern involved-field radiotherapy for lymphoma, based on pretreatment positron-emission tomography data, has resulted in a significant decrease in toxicity, an important consideration in elderly patients.
- Significant comorbidity is a relative contraindication to aggressive treatment in low-risk prostate cancer. Management should be guided by geriatric assessment and life expectancy. For intermediate-risk disease, 4 to 6 months of hormones are combined with external-beam radiotherapy (EBRT). For high-risk prostate cancer, combined-modality therapy is advised.
- For high-intermediate risk endometrial cancer, vaginal brachytherapy alone (rather than EBRT) is recommended as the adjuvant treatment of choice in older patients, without an associated reduction in toxicity.
- Elderly patients with locally advanced rectal cancer benefit from chemoradiation, with prospective data showing that preoperative radiation therapy is associated with significantly better local control and less acute and late toxicity than postoperative radiation therapy.
- For primary brain tumors, shorter courses of postoperative radiotherapy following maximal debulking may provide equivalent survival to longer schedules. The MGMT (O-6-methylguanine-DNA-methyltransferase) methylation status may help to select older patients for temozolomide alone.
- Stereotactic radiosurgery provides an alternative to whole-brain radiotherapy in patients with limited brain metastases. This may be an especially suitable option for older patients at increased risk of cognitive impairment.
- Intensity-modulated radiation therapy is now the standard of care in head and neck cancer and provides an excellent technique to reduce the dose to the carotid arteries, salivary glands, and other critical structures.
Colorectal Cancer
The colorectal cancer guidelines provide a summary of the Task Force report in 2013, to update the existing expert recommendations published in 2009, and include overviews of the recent data on best practice4:
- Embracing the concept of individualized treatment is an absolute requirement for further improvements in the management of patients with colorectal cancer in older patients.
- Multidisciplinary teams are key to enabling individualized treatment. There is a need to utilize some form of geriatric assessment to inform clinical decision-making.
- The potential for comorbidities and the options if serious complications do occur, or treatments fail, should be fully discussed in advance, as the consequences of colorectal surgery can lead to significant quality-of-life issues for older adults, especially when a permanent stoma is required.
- Investigators should be encouraged to design not only clinical trials using low-toxicity treatments that maintain most of the efficacy of full-dose treatments but patient-centered assessments to expand the evidence base in the treatment of older patients with colorectal cancer.
- Radiotherapy can be used effectively to manage inoperable patients as well as in the palliative setting for advanced disease.
Diffuse Large B-Cell Lymphoma
Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma subtype in the elderly and is of increasing prevalence in the older patient population. The newly developed treatment guidelines5,6 address initial therapy for DLBCL, in both limited- and advanced-stage disease, as well as approaches to the relapsed and refractory patient.
Some of the suggestions for optimal care of older patients include the use of alternative regimens for those unable to tolerate R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin, vincristine, and prednisone). Anthracycline-based chemotherapy is complicated by comorbidities and alterations in functional status in older adults, therefore alternative regimens may be considered. At present, there is no clear-cut role for maintenance therapy for DLBCL. In the relapsed setting, there is increasing recognition that select elderly patients may be candidates for high-dose treatment approaches. Geriatric assessment has a role to play in stratifying patients in this setting. Palliative treatment approaches may be considered for those unable to tolerate such therapy.
Taxanes in Breast Cancer
Balancing the efficacy of therapy against toxicity is especially difficult in elderly patients who have diminished physiologic reserve and significant comorbidities. In the adjuvant setting, taxane toxicity is greater in older than in younger patients, but taxanes can be added to anthracylines in healthy high-risk patients or can be used instead of them to reduce cardiac risk. In HER2-positive patients, paclitaxel or docetaxel plus cyclophosphamide is an alternative to anthracylines and reduces trastuzumab (Herceptin)-related cardiotoxicity. In metastatic disease, weekly paclitaxel or three-weekly docetaxel is a cornerstone of treatment. Nab-paclitaxel (Abraxane) offers efficacy comparable to that with solvent-based taxanes, but there are limited study data in the elderly. Neuropathy remains a significant problem.
Radiopharmaceuticals: Focus on the Prostate
Radiopharmaceutical imaging has a clear role in diagnosis and monitoring and involves doses that are pharmacologically inactive. However, the therapeutic use of radionuclides in elderly patients who may be frail and have impaired organ function and bone marrow reserve raises specific issues related to short-term toxicity. On the other hand, limited life expectancy means that elderly patients are less likely than their younger counterparts to be concerned about the long-term consequences of radiation. Efficacy, tolerability, and ease of use are being considered in the context of newly introduced agents, notably the alpha-emitter radium-223 dichloride (Xofigo), which has shown survival benefits in patients with castration-resistant prostate cancer and symptomatic bone metastases.7
Chronic Lymphocytic Leukemia
Elderly patients with CLL do not differ substantially from younger patients with CLL in the stage distribution or molecular biology of their disease, but many are frail, and comorbidities shorten survival independently of factors that are prognostic for CLL. Impaired nutrition and mobility are present in up to 50% of older patients with CLL, and they may not be able to tolerate aggressive therapy. For fit patients, purine-based chemoimmunotherapy remains a standard, with bendamustine (Treanda)/rituximab as an alternative. However, in relapsed or refractory CLL, novel small molecules targeting abnormal signalling in the B-cell receptor pathway are changing management.
For the full guidelines from the Task Forces of the International Society of Geriatric Oncology, visit http://www.siog.org/index.php?Itemid=92. ■
Disclosure: Dr. O’Donovan reported no potential conflicts of interest. For full disclosures of the guideline authors, visit www.siog.org.
References
1. Wildiers H, Heeren P, Puts M, et al: International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol 32:2595-2603, 2014.
2. Droz JP, Aapro M, Balducci L, et al: Management of prostate cancer in older patients: Updated recommendations of a working group of the International Society of Geriatric Oncology. Lancet Oncol 15:e404-e414, 2014.
3. Hoskin P, Sartor O, O’Sullivan JM, et al: Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: A prespecified subgroup analysis from the randomised, double-bline, phase 3 ALSYMPCA trial. Lancet Oncol 15:1397-1406, 2014.
4. Papmichael D, Audisio RA, Glimelius B, et al: Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013. Ann Oncol 26:463-476, 2015.
5. Morrison VA, Hamlin P, Soubeyran P, et al: Approach to therapy of diffuse large B-cell lymphoma in the elderly: The International Society of Geriatric Oncology (SIOG) expert position commentary. Ann Oncol. January 29, 2015 (early release online).
6. Morrison VA, Hamlin P, Soubeyran P, et al: Diffuse large B-cell lymphoma in the elderly: Impact of prognosis, comorbidities, geriatric assessment, and supportive care on clinical practice. An International Society of Geriatric Oncology (SIOG) Expert Position Paper. J Geriatr Oncol 6:141-152, 2015.
7. Kunkler IH, Audisio R, Belkacemi Y, et al: Review of current best practice and priorities for research in radiation oncology for elderly patients with cancer: The International Society of Geriatric Oncology (SIOG) task force. Ann Oncol 25:2134-2146, 2014.
Guest Editor
Dr. Lichtman is an Attending Physician at Memorial Sloan Kettering Cancer Center, Commack, New York, and Professor of Medicine, Weill Cornell Medical College, New York. He is also President Elect of the International Society of Geriatric Oncology (www.siog.org).
