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(Radiology. 1999;211:829-833.)
© RSNA, 1999

Radiation Oncology

Cancer in Patients Aged 90 Years or Older: Radiation Therapy1

Norio Mitsuhashi, MD, PhD, Kazushige Hayakawa, MD, PhD, Michitaka Yamakawa, MD, PhD, Hideyuki Sakurai, MD, PhD, Yoshihiro Saito, MD, PhD, Masatoshi Hasegawa, MD, PhD, Tesuo Akimoto, MD, PhD, Kayoko Hayakawa, MD and Hideo Niibe, MD, PhD

1 Department of Radiology and Radiation Oncology, Gunma University School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. Received August 3, 1998; revision requested September 8; revision received October 9; accepted November 23. Supported in part by a grant-in-aid from the Ministry of Health and Welfare of Japan. Address reprint requests to N.M.


   Abstract
TOP
 Abstract
Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
PURPOSE: To investigate the clinical efficacy of radiation therapy for cancer in patients aged 90 years or older.

MATERIALS AND METHODS: Cancer cases in 32 patients (11 men, 21 women) aged 90 years or older who underwent radiation therapy in 1970–1997 were retrospectively analyzed. The mean patient age was 92.2 years, with a range of 90–98 years. Head and neck cancer (n = 14 [44%]) and skin cancer (n = 6 [19%]) were the most common.

RESULTS: Eleven (79%) of the 14 patients with head and neck cancer were treated with curative intent. Radiation response without any severe complication was observed in nine (90%) of the 10 patients with head and neck cancer treated with curative intent who finished treatment. The median survival time was 8 months (range, 3–55 months) in the 10 patients with head and neck cancer who completed treatment with curative intent. Complete response was achieved in all of the patients with skin cancer without any major sequelae. Complete response was also observed in all three of the patients with non-Hodgkin lymphoma, but two patients treated with adjuvant chemotherapy died of drug-induced pneumonitis. Palliation was achieved in all nine of the patients treated with palliative intent.

CONCLUSION: Age of 90 years or older is not a limiting factor for radiation therapy.

Index terms: Aging • Genitourinary system, therapeutic radiology, 80.1299, 80.32 • Head and neck neoplasms, therapeutic radiology, 20.1299, 20.32, 20.33 • Lymphoma, therapeutic radiology, 99.1299, 99.32 • Skin, therapeutic radiology, 20.1299, 20.32, 43.1299, 43.3289 • Therapeutic radiology, 20.1299, 43.1299, 99.1299


   Introduction
TOP
 Abstract
 Introduction
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
The population aged 65 years or older has recently exceeded 14.8% of the Japanese population and will reach 27.4% in 2025 (1). The mean life expectancy in Japan became 77.2 years for male and 83.8 years for female persons in 1997 and is the longest in the world (1). In 1995, the percentages of male and female persons aged 90 years or older were 0.2% and 0.6%, respectively (1). In addition, cancer has become a leading cause of death in Japan; 275,000 people died of cancer in 1997 (1).

Among the population of persons 90 years or older, cancer took fourth place among causes of death; about 9,000 patients die of cancer each year (1). Elderly cancer patients are, however, commonly treated in a less aggressive fashion than younger patients due to their shorter life expectancy or because of associated medical problems (1). Surgery, chemotherapy, or radiation therapy may be of benefit to individuals 90 years or older, depending on the tumor type, stage, and clinical criteria (resectability, performance status, coexistent morbidity, etc), but many physicians hesitate to treat them radically. We have already reported that age was not a limiting factor for radiation therapy in the treatment of elderly patients with lung cancer, esophageal cancer, or cervical cancer (2–5). Many articles have been published about the efficacy of radiation therapy in a population of less elderly patients (6–10).

To our knowledge, there are few data in the literature concerning the effectiveness and the complications of radiation therapy for the most elderly patients, although the growing population of the oldest means that in the near future there will more of them treated with radiation therapy (3,11–13). In this study, we retrospectively investigated the clinical efficacy of radiation therapy for patients aged 90 years or older with cancer at the Gunma University Hospital, Japan, between 1970 and 1997.


   MATERIALS AND METHODS
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 References
 
Records from the Department of Radiology and Radiation Oncology at Gunma University Hospital were reviewed to identify patients who underwent radiation therapy and who were aged 90 years or older.

From 1970 through 1997, 32 patients aged 90 years or older received radiation therapy for various malignant tumors (Table 1). There was no patient aged 90 years or older treated with radiation therapy until 1977.


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  		TABLE 1. Primary Cancer
 
Twenty-three patients were treated with curative intent, and the remaining nine patients were treated with palliative intent. Informed consent was obtained from all patients included in the study.

There were 11 men and 21 women. The mean age for the men was 91.7 years, with an age range of 90–96 years; the mean age for the women was 92.5 years, with an age range of 90–98 years. Cancer in all the patients was classified and staged according to the Union Internationale Contre le Cancer TNM classification and stage grouping, except for malignant lymphoma, which was staged according to the Ann Arbor classification.

At the beginning of treatment, the performance status was 0 or 1 in 17 (74%) patients treated with curative intent but was 0 or 1 in only four (44%) patients treated with palliative intent, on the basis of the World Health Organization classification. The prevalence of a performance status of 3 or 4 was 9% (two patients) for the patients treated with curative intent and 33% (three patients) for the patients treated with palliative intent. Twenty (62%) patients had coexistent illnesses. Fourteen patients had cardiovascular disease such as hypertension, coronary artery disease, or congestive heart failure. Three patients had cerebrovascular disease. Three patients had a past history of other malignancy. Two patients had chronic obstructive pulmonary disease. One had gastrointestinal disease. One had diabetes mellitus. Four patients had at least three medical problems—cancer and two others.

Our treatment policy of curative radiation therapy for the elderly has been described elsewhere (5). In brief, the conventional external-beam radiation therapy was delivered with 6- or 10-MV x rays or cobalt 60 {gamma} rays. Although the radiation therapy technique was not changed because of age, a minimum curative dose with a limited radiation field was administered for patients treated with curative intent to reduce acute sequelae. Split-course irradiation was used intentionally in patients with head and neck cancer who developed moderate or severe mucositis. Chemotherapy was not administered in combination with radiation therapy, except in patients with malignant lymphoma.

We made an effort to keep the hospital stay as short as possible and to treat patients on an outpatient basis because, to our knowledge, the elderly have a limited ability to adapt to changes in lifestyle. Hypofractionated electron-beam therapy, with a total dose of 39.0 Gy administered over 3 weeks, was often used, especially for those with skin cancer, to shorten the overall treatment time and to make it possible to treat on an outpatient basis. Fraction size was 6.5 Gy, with two fractions per week (14–16). Although our general radiation therapy policy for the elderly has been described above, radiation therapy was individualized for the tumor stage and configuration, age, past history of the disease, and general status of the patient.

Palliative radiation therapy was performed to relieve pain in four patients, to stop bleeding in two patients, and to improve dysphagia in one patient. The radiation field for palliative radiation therapy usually covered only the symptomatic organ or site, with a minimal margin. The radiation dose was 12.0–61.4 Gy.

The evaluation of the local response to radiation therapy was based on the results of physical examination, radiography, and/or endoscopy. The use of findings of computed tomography has gradually increased since 1982. For patients irradiated with curative intent, tumor response was classified into one of four grades according to the following criteria. Complete response was complete regression of the clinical disease. Partial response was more than 50% reduction in tumor bulk but less than 100% resolution of disease. No change was a less than 50% reduction or a less than 25% increase in tumor size. Progressive disease was defined as a 25% or greater increase in tumor size. Radiation response was represented as the relief from symptoms.

The Radiation Therapy Oncology Group scoring criteria (17) of acute and late reactions to radiation therapy were used to evaluate radiation toxicity.

All patients were followed up periodically. Survival time was calculated from the date of the initiation of radiation therapy to the date of the last follow-up examination.


   RESULTS
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 References
 
Radiation therapy was completed in 22 (96%) of the 23 patients treated with curative intent, except in a patient with carcinoma of the hard palate. She refused to continue radiation therapy because she wanted to stay at home with her family. Complete response was achieved in 14 (64%) of the 22 patients. Partial response and no change were observed in four (18%) and three patients (14%), respectively. The overall response rate was therefore 82%. In one patient who underwent excisional biopsy of skin cancer before radiation therapy, radiation response could not be evaluated. Acute reactions, including mucositis and dermatitis, were observed, as mentioned in Results, Skin Cancer, but there was no difference in the intensity or duration of these reactions compared with the intensity or duration in younger patients.

The planned doses were delivered in all of the patients who were treated with palliative intent, and palliation was achieved in all patients.

Head and Neck Cancer
Radiation therapy was performed in 14 patients with head and neck cancer; the distributions of the primary site and clinical stage are shown in Table 2. Eight (57%) patients had stage IV disease. Eleven (79%) patients were treated with curative intent. Table 3 summarizes the therapeutic response of patients treated with curative intent. One of the 11 patients refused radiation therapy after a total dose of 6.0 Gy had been administered. The median total dose for the 10 patients treated with curative intent was 61.2 Gy, with a range of 35.0–78.0 Gy. Radiation therapy was interrupted for 2–3 weeks due to grade 2 or 3 mucositis in four patients. The remaining six patients completed the planned course of radiation therapy without any severe complication.


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  		TABLE 2. Primary Site and Stage of Head and Neck Cancer
 

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  		TABLE 3. Radiation Response in Patients with Head and Neck Cancer Treated with Curative Intent
 
Radiation response was observed in nine (90%) of the 10 patients, with a complete response in six (60%) of the 10 patients. The median survival time in the 10 patients who completed treatment with curative intent was 8 months, with a range of 3–55 months. All the patients have died, but the six patients who had a complete response died of other disease without evidence of tumor recurrence. Three patients were able to survive for more than 20 months.

Palliation was achieved in all three patients treated with palliative intent, and median survival was 6 months. Two patients had relief from pain of swallowing. In the other patient, who had huge lymph node metastasis, local pain control was obtained at a total dose of 40.0 Gy, although a grade 1 acute skin reaction developed.

Skin Cancer
Six patients with squamous cell carcinoma of the skin, including a patient treated with palliative intent, received radiation therapy. One patient (patient 4 in Table 4) underwent excisional biopsy before irradiation. The patient and treatment characteristics are summarized in Table 4. As described before, skin cancer was treated mainly with hypofractionated electron-beam radiation therapy. The median total dose in the five patients treated with curative intent was 45.5 Gy, with a range of 32.0–72.0 Gy. Complete response was achieved in all of the patients, and no local-regional recurrence was observed. The median survival of the five patients treated with curative intent was 23 months, with a range of 6–38 months.


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  		TABLE 4. Characteristics of Patients with Squamous Cell Carcinoma of the Skin
 
Grade 1 and 2 acute skin reactions were observed in three and three patients, respectively, but they were acceptable reactions. One patient (patient 1 in Table 4) developed patchy skin atrophy (grade 2 chronic skin reaction).

Non-Hodgkin Lymphoma
The characteristics of the three patients with non-Hodgkin lymphoma are shown in Table 5. Complete response was observed in all patients, but two patients treated with a combination of radiation therapy and chemotherapy died immediately after the initiation of adjuvant chemotherapy due to drug-induced pneumonitis. Grade 1 acute oral mucositis was observed in one patient (patient 1 in Table 5). This patient treated with radiation therapy alone survived for 7 years.


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  		TABLE 5. Characteristics of Patients with Non-Hodgkin Lymphoma
 
Urogenital Malignancy
Table 6 shows the characteristics of the three patients with urogenital malignancy. A patient with bladder cancer underwent radical cystectomy because of a residual tumor after local radiation therapy but died of surgery-related morbidity. She developed grade 1 acute cystitis during radiation therapy but tolerated it well. A patient with penile cancer was successfully treated with brachytherapy by using a silicon mold (18) and survived for 6 years without evidence of a tumor or treatment-related complication. In a patient with prostate cancer with bone metastases, pain relief was achieved by means of radiation therapy, with a total dose of 24.0 Gy.


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  		TABLE 6. Characteristics of Patients with Urogenital Cancer
 
Miscellaneous Malignancies
A patient with esophageal cancer and a patient with liposarcoma in a lower limb were treated with curative intent. The patient with esophageal cancer had a partial response but died of uncontrolled cancer 6 months after radiation therapy. The patient with liposarcoma, who had no change, had survived for 54 months without progression of the tumor but had developed a grade 1 chronic skin reaction.

The remaining four patients (with a soft-tissue tumor, carcinoma of the uterine corpus, esophageal cancer, and metastatic bone tumor) were successfully treated with palliative intent without intolerable acute sequelae (stopping of bleeding from the tumor, two patients; improvement of dysphagia, one patient; and pain relief, one patient).


   DISCUSSION
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
References
 
The distribution of primary sites in patients aged 90 years or older treated with radiation therapy was different from that reported previously in patients aged 80 years or older (5). Head and neck cancer (29%), lung cancer (15%), esophageal cancer (14%), and cervical cancer (14%) were the four leading cancers in patients aged 80 years or older, whereas head and neck cancer (44%), skin cancer (19%), malignant lymphoma (9%), and urogenital cancer (9%) were the four leading cancers in patients aged 90 years or older.

We have few precise data available on whether the very old (those aged 90 years or older) should be treated aggressively or whether age may correlate with the tolerance or response to radiation therapy. This lack of information may lead the radiation therapist to alter or to interrupt a course of radiation therapy in the treatment of the most elderly. We have reported that the elderly with lung cancer, esophageal cancer, or cervical cancer were able to complete curative radiation therapy without serious complications, and the radiation effectiveness in them was comparable to that observed in younger patients (2–5). Recently, some investigators reported that radiation therapy is also effective and well tolerated by patients 80 years of age or older and that age is not a limiting factors for radiation therapy (3,11,12,19,20). Oguchi et al (13) also reported that age over 90 years did not affect the effectiveness of radiation therapy and patient tolerance.

Lusinchi et al (7) and Chin et al (21) reported that no significant relationship between age, general status, and the treatment outcome could be observed in head and neck cancers in patients older than 70 years. In our series, the distribution of primary sites of head and neck cancer differed from that in younger patients, and the patients aged 90 years or older had a higher prevalence of oral cavity cancer (5). Except for patients with laryngeal cancer, four of eight patients who underwent curative radiation therapy had to have a rest due to acute mucositis. However, the tolerance of radiation therapy and subsequent repair of radiation damage to the oral mucosa did not appear to differ from those in a younger population. All of the patients who had to have a rest due to acute mucositis could resume radiation therapy with a rest of less than 3 weeks. A 60% complete response rate was achieved, which is similar to that observed in a younger population. Unfortunately, findings of this study could not clarify the failure pattern and late complications because most of the patients who had a complete response did not survive long enough to develop recurrence or late sequelae.

Hypofractionated electron-beam radiation therapy was used for skin cancer to shorten the overall treatment time. All patients treated with curative intent were successfully irradiated in short-course treatment with 6.5-Gy fractions twice a week. As reported previously (15,16), we designed this fraction schedule first for chest wall recurrence of breast cancer and have applied this method mainly to head and neck cancer, skin cancer, and cervical cancer, with a high local control rate.

Conventional radiation therapy with a total dose of 60.0–70.0 Gy in 6–7 weeks has also been recommended for curative treatment for the elderly, but most elderly patients with poor performance status do not tolerate such treatment without deterioration of their quality of life. Short overall treatment time for hypofractionated regimens has advantages for the most elderly in spite of a risk of associated acute and late reactions (22).

Although we treated only two patients with esophageal cancer in this series, we have published the treatment results for esophageal cancer in patients older than 80 years (3). The 5-year disease-free survival rates for all patients treated with curative intent and for patients who had complete response were 34% and 64% without severe complications, respectively (3).

We had no patient who underwent abdominal or pelvic irradiation curatively. Zachariah et al (11) reported that, due to diarrhea and vomiting, the treatment interruption was highest in patients who underwent abdominal or pelvic irradiation with large fields and that reduction of the field size might make radiation therapy even safer and more effective in abdominal and pelvic tumors for elderly patients aged 80 years or older. Pignon et al (9,10) reported that thoracic and pelvic irradiation was performed safely in the elderly.

In conclusion, these findings suggest that age was not a limiting factor for radiation therapy in patients aged 90 years or older. Radiation therapy will play an increasingly important role in the treatment of the oldest patients with cancer.


   Footnotes
 
Author contributions: Guarantor of integrity of entire study, H.N.; study concepts, N.M., H.N.; definition of intellectual content, N.M.; literature research, N.M., Kazushige Hayakawa., M.Y., H.S.; clinical studies, N.M., Kazushige Hayakawa, M.Y., H.S., Y.S., M.H., T.A., H.N.; data acquisition and analysis, N.M., Kayoko Hayakawa; manuscript preparation and editing, N.M.; manuscript review, H.N.


   References
TOP
 Abstract
 Introduction
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 

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