As one might expect, the focus on older patients developed in surgical and radiation oncology at the same time as in medical oncology. As we have done in our overview of medical oncology, we may recognize a prehistory, past history, and present history in surgical and radiation geriatric oncology.
Since the beginning of the past century, advanced chronologic age was considered a prognostic and predictive factor in surgical oncology. In a second period dating approximately to the mid-1990s, clinicians began to consider the influence of functional age and comorbidity on the management of the older person. At that time, the evaluation of functional age became central to management decisions. In the third period, prospective surgical trials with consideration of geriatric parameters and the involvement of geriatricians were initiated.
In the first period, it was established that advanced age was associated with a worse prognosis in potentially operable patients with breast cancer1 and colorectal cancer.2 It also became clear that the incidence and prevalence of cancer in older patients were increasing with the aging of the population, and older patients were denied appropriate treatment more often than younger ones.3
Following a call to action by Ian S. Fentiman, MD,3 the assessment of functional age and comorbidity was inaugurated by Riccardo Audisio, MD, in Europe and by Peter Fabri, MD, in the United States. In 1997, Audisio et al highlighted the influence of resilience on the outcome of elective surgery for gastrointestinal tumors and addressed the financial issues associated with the management of the older population.4,5
In 1998, Fabri6 wrote that a surgical procedure in older patients must be planned with consideration of the difference in physiology and response to anesthesia and stress, with particular attention given to nutritional issues. This statement was made in the textbook Comprehensive Geriatric Oncology, which dealt extensively with the surgical management of common solid tumors. The general conclusion was that age did not warrant alterations in techniques. Instead, patient selection based on resilience was the key to optimal outcome.
In a review of surgical oncology issues,7 Dr. Audisio and Andrew Zbar, MD, showed how prejudice regarding operative risks and long-term outcomes might have deprived elderly patients of life-saving treatment. In this review, specific epidemiologic data were presented, treatment procedures discussed, and the effectiveness of follow-up protocols were analyzed together with cost-effectiveness and quality-of-life issues.
In 2004, the recommendation of the International Society of Geriatric Oncology (SIOG) task force on the surgical management of elderly cancer patient was published by Audisio et al.8 After highlighting the latest updates and trends specifically related to solid tumors in senior patients with cancer, they stressed the crucial point at that time: the want of a reliable instrument for risk assessment before surgery and of an active participation of geriatricians in management.
We can speculate that the third period (the present history) involves the development of instruments to evaluate geriatric parameters before surgery. As such, it began around the half of the first decade of the new millennium with the validation by Audisio et al of an instrument that combined elements of the comprehensive geriatric assessment and the American Society of Anesthesiologists (ASA)-defined operative risk called preoperative assessment of cancer in the elderly (PACE).8 PACE facilitated the decision concerning the eligibility of elderly patients with cancer for surgical intervention and reduced the chances of inappropriate age–related inequity in access to surgical intervention. It was recommended that PACE be used routinely in surgical practice.
In subsequent years, this contribution was followed by a multicenter study on the Preoperative Risk Estimation in Oncogeriatric Surgical Patients (PREOP) risk score to provide an objective measure on which to base decisions.9 The PREOP was based on three common geriatric screening tools: the Timed Up and Go test, Nutritional Risk Screening, and the ASA classiﬁcation.
In older candidates for surgical procedures, the contribution of geriatricians to the decision is paramount. In 2014, at Memorial Sloan Kettering Cancer Center, geriatricians were involved in evaluating older individuals before major surgery for the first time.10 This approach resulted in a significant reduction in acute surgical complications such as delirium as well as long-term issues such as disability.
Radiation treatment, a local type of cancer treatment without the risk of surgical complications, appeared to be a reasonable alternative to surgery in older patients with cancer. In 1991, Wickoff et al11 reviewed the results of partial mastectomy and postoperative breast irradiation in women aged 65 years and older at the Moffitt Cancer Center; they found that radiation was as well tolerated by older women as it was by younger patients. Prior to this study, many older women were excluded from postoperative irradiation, and in general, older age was considered a risk factor for the complications of radiation.
In 1991, Pierre Scalliet, MD,12 observed there was insufficient information to form the basis for guidelines for radiation practice in elderly patients. In considering the use of radiotherapy in such patients, three major questions needed to be addressed: the natural course of cancer in relation to age, the tolerance of radiotherapy, and a decision analysis of risks and benefits. The main concern was about the utilization of combined chemoradiation, which appeared particularly risky.
“In 1994, GROG started a number of prospective studies to assess the characteristics of each elderly patient with cancer referred to radiotherapy centers … and the main characteristics of the tumors.”— Silvio Monfardini, MD; Lodovico Balducci, MD; Janine Overcash, PhD, APRN-CNP, FAANP, FAAN; and Matti S. Aapro, MD
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One of the first cooperative groups to focus on cancer in the elderly was the Italian Geriatric Oncology Group (GROG), headed by the radiation oncologists Giampiero Ausili-Cefaro, MD, and Patrizia Olmi, MD. In 1994, GROG started a number of prospective studies to assess the characteristics of each elderly patient with cancer referred to radiotherapy centers (eg, age, gender, performance status, comorbidity, activities of daily living, family status) and the main characteristics of the tumors.13 GROG has unfortunately discontinued its activity, but it still represents a lasting model of cooperative research in older individuals.
In the same year, Scalliet et al14 published a contribution to the book Cancer in the Elderly: Treatment and Research. The authors again observed that despite the scarcity of data, age did not seem to be a risk factor for therapeutic complications. Well-planned fractionation might have permitted safe radiation treatment of cancer in most elderly patients. They emphasized the logistic problems such as daily access to a radiation center.
In 1998, Pignon and Scalliet15,16 recognized that ageism—the unsubstantiated prejudice that age implied a condition of frailty—had compromised proper radiation treatment in the elderly, as it had done for surgical and medical treatments. In clinical practice, advanced age could result in undertreatment, even though patients may have had no other illness and no functional impairment. Some comorbid conditions that occur more frequently in older patients could complicate the outcome of treatment. However, overall, treatment schedule alterations based on comorbidity or functional conditions were rare. The risk of acute complications for different types of tumors was the same for older and younger patients. These authors also stressed that available studies at that time did not support the indiscriminate reduction of radiation dose or intensity for older patients.
In 2004, the GROG reported the results of trials carried out during 15 years in patients older than 70 years.17 The tumor sites considered were the larynx, lung, breast, prostate, rectum, endometrium, and bladder. Overall, 31% were given radiotherapy alone with curative intent, 27% received radiotherapy before or after surgery and/or chemotherapy, and 42% were treated with palliative intent. There was no major difference between the planned and delivered doses. Mean doses for palliation treatments in older patients were similar to those usually delivered to younger adults. Mean doses for cure were lower than those in younger subjects. The conventional daily fractionations were the most commonly used. Nonconventional fractionations were usually reserved for palliation.
Acute toxicity reported in the GROG studies was shown to be negligible, even if differentiated according to the site and type of disease. Toxicity-associated radiotherapy discontinuation was irrelevant, considering that only 3% presented with grade 3 or 4 of toxicity according to the Radiation Therapy Oncology Group scale and had to discontinue treatment for a few days. The conclusion was that treatment modalities were quite similar to those used in younger patients, and tolerance was good in the majority of elderly individuals with cancer.
As for local tumor control, there was no evidence that neoplasms of the elderly responded differently. Age per se did not seem to be a contraindication for the implementation of radiotherapy, whose modalities were similar to those used in younger subjects. Clearly, these considerations were valid for elderly patients in good general condition and acceptable comorbidity. Additional information was believed to be required for patients affected by serious multimorbidity and functional or social limitations.
The GROG authors stated that the oldest old—over 80 years—should be carefully evaluated before any antineoplastic management. In this respect, the cooperation with geriatricians seemed of the utmost importance. In the following years, the development of the multidisciplinary approach of geriatric oncology has also involved radiation oncologists and has stimulated research on the best technologic advances, providing new curative options for older patients with cancer, with a possible reduction in treatment toxicity.
An article published by an SIOG Task Force summarized the progress achieved in the field of radiotherapy in various tumor types occurring in older patients in the 15 years from 1998 to 2014, and the authors made recommendations for curative radiotherapy in older patients.18 Evidence-based guidelines were provided for breast, lung, endometrial, prostate, rectal, pancreatic, esophageal, head and neck, and central nervous system malignancies and lymphomas.
The authors noted that patient selection should include comorbidity and geriatric evaluation. They stated that conventional radiotherapy was a preferred treatment for many elderly patients, given that it caused less toxicity than systemic therapy or surgery. Technologic advances had improved radiation effectiveness while reducing morbidity, sometimes providing new curative treatment options for elderly patients. Moreover, advances in radiation planning and delivery improved target coverage, reduced toxicity, and led to wide eligibility for treatment. Shorter courses of hypofractionated whole-breast radiotherapy were safe and effective.
Conformal radiotherapy and involved-field techniques without elective nodal irradiation improved outcomes in non–small cell lung cancer (NSCLC) without increasing toxicity. Where comorbidities precluded surgery, stereotactic body radiotherapy was an option for early-stage NSCLC and pancreatic cancer. Modern involved-field radiotherapy for lymphoma based on pretreatment positron-emission tomography data reduced toxicity.
It was recognized that significant comorbidity was a relative contraindication to aggressive treatment in low-risk prostate cancer. For intermediate-risk disease, 4 to 6 months of hormone therapy was recommended, combined with external-beam radiotherapy. For high-risk prostate cancer, combined-modality therapy was advised. For high-intermediate–risk endometrial cancer, vaginal brachytherapy was recommended. Short-course external-beam radiotherapy was considered an alternative to combined-modality therapy in older patients with rectal cancer without significant comorbidities. Endorectal radiotherapy could be an option for early disease.
For primary brain tumors, shorter courses of postoperative radiotherapy following maximal debulking provided equivalent survival to longer schedules. Stereotactic radiotherapy could provide an alternative to whole-brain radiotherapy in patients with limited brain metastases. Intensity-modulated radiation therapy could provide an excellent technique to reduce the dose to the carotids in head and neck cancer, and this approach improved locoregional tumor control in esophageal cancer. Best practice and research priorities were also summarized. ν
DISCLOSURE: The authors reported no conflicts of interest.
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In part 1 of this three-part article, which was published in the October 10, 2020, issue of The ASCO Post, we chronicled the progress made in geriatric oncology up to the decade of the 1990s, which saw an explosion of research activity in the study of aging and cancer. In part 2, we review the...