Radiotherapy for Japanese elderly patients with cervical cancer: preliminary survival outcomes and evaluation of treatment-related toxicity
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Abstract
Purpose
To examine the preliminary survival outcomes and treatment-related toxicity for elderly patients with cervical cancer treated with radiotherapy (RT).
Methods
Forty patients ≥75 years old with cervical cancer who were treated with RT were evaluated. Of these 40 patients, 25 were classified as FIGO stage I or II and 15 as stage III or IVA. Thirty-five patients were treated with radical RT (RRT), and five were treated with surgery plus adjuvant RT (S + ART). External beam radiotherapy combined with high-dose-rate intracavitary brachytherapy was performed on 31 patients who were treated with RRT and on 2 patients who were treated with S + ART because of positive vaginal surgical margins. The patients’ median age was 78 years (range 75–89 years). Concurrent chemotherapy (CCT) was performed on five patients (RRT: 3, S + ART: 2).
Results
The median follow-up period was 20 months (range 1–85 months). Only one patient could not complete RT. The 3-year overall and disease-specific survival (OS and DSS) rates for all patients were 58 and 80%, respectively. Five patients experienced Grade 3 acute toxicity; two were treated with RRT (2/35), and three were treated with S + ART (3/5, 2 of them with CCT). Two patients experienced Grade 3 late toxicity; one was treated with RRT (1/35, with CCT) and the other was treated with S + ART (1/5). No Grade 4 or higher toxicity was experienced.
Conclusions
RRT for elderly patients with cervical cancer is generally effective and safe, but severe toxicity may occur with more aggressive treatment modalities.
Keywords
Cervical cancer Radiotherapy Elderly patients Treatment-related toxicityIntroduction
The population of elderly people has been rapidly increasing in Japan. According to statements by the Ministry of Health, Labor and Welfare, the average life expectancy for men and women in 2008 was 79 and 86 years old, respectively [1]. In particular, the life expectancy of a Japanese woman is the longest in the world. With an increasingly aged society, the number of elderly patients with various malignancies continues to increase. In addition, the number of younger cancer patients has also been increasing due to changes in lifestyle and viral infections. In Japan, malignant neoplasms have the highest mortality rate, surpassing cerebrovascular and heart diseases in 1981.
For cervical cancer, the most commonly afflicted age group is women in their late 30s to early 40s; the affliction of young women is usually emphasized [2, 3, 4]. However, the incidence of cervical cancer increases again after age 70, and the mortality rate increases with age. Therefore, the increase in the ratio of elderly patients with cervical cancer must be evaluated, and an appropriate treatment modality should be identified. Surgery and/or radiotherapy (RT) are the radical treatment modalities for cervical cancer. For advanced-stage disease, RT with or without concurrent chemotherapy (CCT) is usually the radical treatment of choice. For early-stage disease, the survival outcomes of surgery and RT are known to be similar [5, 6, 7, 8]. Although RT seems to be a less invasive treatment, its long-term complications and negative impact on sexual function when compared with surgery are important considerations for younger patients [9, 10, 11]. Therefore, there is a trend emerging in which surgery is usually used for younger patients and RT is used for elderly patients. However, although it is obvious that RT plays an important role in the treatment of most stages (I–IVA) of cervical cancer, the recent increase in the elderly population may further increase RT’s importance [12, 13].
In this study, we retrospectively analyzed the preliminary survival outcomes and evaluated treatment-related toxicity for Japanese elderly patients (≥75 years old) with cervical cancer treated with RT.
Materials and methods
Patients
Patient information according to clinical factors
| Factors | Number of patients (total = 40) | % |
|---|---|---|
| Treatment period | ||
| 2000–2005 | 9 | 22.5 |
| 2006–2009 | 31 | 77.5 |
| Age (years old) | ||
| ≤80 | 27 | 67.5 |
| >81 | 13 | 32.5 |
| Median age (range) | 78 (75–89) | |
| Karnofsky performance scale score | ||
| >70 | 20 | 50 |
| 50–70 | 17 | 42.5 |
| <50 | 3 | 7.5 |
| Stage (FIGO) | ||
| IA | 1 | 2.5 |
| IB | 4 | 10 |
| IIA | 7 | 17.5 |
| IIB | 13 | 32.5 |
| IIIA | 2 | 5 |
| IIIB | 11 | 27.5 |
| IVA | 2 | 5 |
| Histology | ||
| SCC | 38 | 95 |
| Adenocarcinoma | 2 | 5 |
| Nodal metastasis | ||
| Yes | 6 | 15 |
| No | 34 | 85 |
| Medical complications | ||
| Yes | 29 | 72.5 |
| No | 11 | 27.5 |
| History of other cancers | ||
| Yes | 4 | 10 |
| No | 36 | 90 |
Treatment
Patient distribution per treatment modality
| Number of patients | Use of CCT | |
|---|---|---|
| RRT | ||
| EBRT + HDR-ICBT (with nodal boost) | 31 (2) | 3 |
| EBRT (with local boost) | 3 (2) | 0 |
| HDR-ICBT | 1 | 0 |
| S + ART | ||
| EBRT | 3 | 1 |
| EBRT + ICBT | 2 | 1 |
The patients who received EBRT combined with HDR-ICBT were initially treated with whole pelvic irradiation using a box field and high-energy 10 MV X-ray photons from a linear accelerator with a daily fraction size of 1.8–2.0 Gy delivered five times per week. A centrally shielded field using anterior/posterior opposed portals was applied just before starting HDR-ICBT. The patients who received EBRT alone were also initially treated with whole pelvic irradiation. A boost to the primary tumor was delivered using a three-dimensional conformal technique, and a pelvic lymph node boost was delivered using the anterior/posterior opposed portals. The median total dose of EBRT was 50.4 Gy (range 16.2–61.2 Gy). The HDR-ICBT was done with a Microselectron HDR (Nucletron, The Netherlands) using a 192-Iridium remote afterloading system at 1-week intervals during the period of EBRT. The median total dose to point A was 20.0 Gy (range 4.5–31.0 Gy) with a single fraction size of 4.0–6.5 Gy. Treatment planning for HDR-ICBT was performed at each irradiation using PLATO Brachytherapy Planning System version 3.2 (Nucletron, The Netherlands). Evaluation of the rectal and bladder dose was performed according to ICRU Report 38 [15].
Follow-up, evaluation of treatment-related toxicity, and statistical analysis
After completion of their treatment, most patients were followed up by gynecological and radiation oncologists every month during the first year, primarily because elderly patients tolerate RT less well and unexpected toxicity might be experienced. However, patients who lived far from our institution were followed up every 2–3 months. Afterward, follow-up was conducted every 3–6 months to detect recurrence and late toxicity. A gynecological examination was performed, and the tumor marker was checked at every visit. SCC Antigen was used for patients who had SCC, and Carcinoembryonic Antigen (CEA) was usually used for patients who had adenocarcinoma. Radiographic examinations (CT scan or MRI) were performed as necessary.
Both acute and late treatment-related toxicity were evaluated using medical records and CTC-AE version 4.0 [16]. Acute toxicity was defined as those events that occurred within 90 days from the start of the treatment, and late toxicity was defined as those events that either occurred >90 days from the start of the treatment or persisted beyond 90 days.
Statistical analyses were performed using Sigma Plot 9.0 software (Systat Corporation, CA, USA). Survival rates were calculated with the Kaplan–Meier method and compared with the use of log-rank test. The follow-up period was calculated from the start of the treatment. P values <0.05 were considered statistically significant.
Results
Patient status and patterns of failure
The median follow-up period for all patients was 20 months (range 1–85 months). The median follow-up period for survivors was also 20 months (range 6–85 months). Of the initial 40 patients, 38 completed the treatment as planned, 1 completed with a delay due to concomitant heart disease, and 1 could not complete the treatment because of acute toxicity. These two patients who experienced delay or cancellation had lower KPS scores (<50). Seven patients experienced recurrence: four locally, one in the para-aortic lymph nodes, one distantly, and one with only tumor marker (SCC Antigen) elevation. Even though a thoracic-abdominal contrast enhanced CT scan, a pelvic MRI, a gynecologic examination and cytology were performed, a recurrent tumor could not be detected at any site. However, this patient was presumed to have microscopic recurrence because SCC Antigen increased continuously. Regarding the clinical stages, one patient was classified as IIA, one as IIIA, and five as IIIB. Six of the seven patients with recurrence were treated with RRT, and one was treated with S + ART. During the period of this study, nine patients died. Among them, five died because of the primary disease, and four died from other causes. The patient who could not complete the treatment had persistent disease and died of the primary disease. Of the remaining two patients who experienced recurrence, one with the para-aortic lymph nodes metastases is alive with the disease and one with tumor marker elevation apparently died from a different cause. The patient who had early-stage lung cancer concurrently with the cervical cancer received the left lower lobe resection after completion of RT. The pathological diagnosis was adenocarcinoma, pT2N0M0. This patient experienced multiple bone metastases (bilateral sacroiliac joints and lumber spine) about 22 months after surgery. Bisphosphonate has been continuously administered, and the patient is doing well without pain.
Preliminary survival outcomes
Preliminary overall and disease-specific survival (OS and DSS) rates for all patients (n = 40) using the Kaplan–Meier method with a median follow-up of 20 months (range 1–85 months). The 3-year OS and DSS rates were 58% (a) and 80% (b), respectively
Treatment-related toxicity
Acute treatment-related toxicity according to treatment modality (CTC-AE version 4.0)
| RRT (use of CCT), total: 35 | S + ART (use of CCT), total: 5 | |
|---|---|---|
| Gastrointestinal | ||
| Grade 1–2 | Diarrhea: 16 (2), gastrointestinal pain: 2 | Diarrhea: 1(1) |
| Grade 3 | Diarrhea: 1 | Intestinal infection: 1(1)a, intestinal obstruction: 1 |
| Grade 4 | 0 | 0 |
| Genitourinary | ||
| Grade 1–2 | Urinary frequency: 3, cystitis: 1 | Urinary tract obstruction: 1 |
| Grade 3 | Cystitis: 1 | Cystitis: 1, urinary tract obstruction: 1(1)a |
| Grade 4 | 0 | 0 |
Late treatment-related toxicity according to treatment modality (CTC-AE version 4.0)
| RRT (use of CCT), total: 35 | S + ART (use of CCT), total: 5 | |
|---|---|---|
| Gastrointestinal | ||
| Grade 1–2 | Rectal bleeding: 2 | 0 |
| Grade 3 | 0 | Intestinal obstruction |
| Grade 4 | 0 | 0 |
| Genitourinary | ||
| Grade 1–2 | Cystitis: 2 | 0 |
| Grade 3 | Cystitis: 1(1) | 0 |
| Grade 4 | 0 | 0 |
| Other | ||
| Grade 1–2 | Lymphedema: 2 | Lymphedema: 1 |
| Grade 3 | 0 | 0 |
| Grade 4 | 0 | 0 |
Discussion
Choosing a treatment for elderly patients with various malignancies is usually difficult. Careful evaluation of their general condition and concomitant medical problems must be performed before the treatment begins. Compared with young patients, safer and more effective modalities should be chosen because severe toxicity may lead to cancellation or delay of the treatment and subsequent loss of quality of life [17, 18, 19, 20, 21]. Generally, RT is thought to be less invasive than surgery or chemotherapy. Moreover, with recent technical developments, a reduction of radiation-related toxicity has been achieved, and the safety of RT is increasing markedly. Therefore, RT is usually chosen for elderly patients as a single modality, although sometimes RT is combined with surgery and/or chemotherapy. Certainly, RT has taken on a greater role in aging societies such as Japan. For example, in this study, just 9 patients were treated from 2000 to 2005, but 31 were treated from 2006 to 2009.
Although there are several large retrospective studies that have analyzed treatment results and prognostic factors, whether age is a negative prognostic factor remains controversial [12, 13, 22, 23, 24, 25, 26, 27]. However, most reports have demonstrated that RT is effective for elderly patients. For example, Ikushima et al. analyzed 727 patients with cervical cancer and reported that the 5- and 10-year disease-specific survival rates of 132 patients aged ≥75 years were 66 and 57%, respectively. Thus, age was not a significant prognostic factor in that study [13]. Chen et al. analyzed a total of 295 patients. They reported that the 5-year cause-specific survival rates of 79 patients aged ≥70 years with respect to FIGO stage were 100% for IB, 85% for IIA, 78% for IIB, and 42% for III. Thus, again age was not a significant prognostic factor in this case [26]. On the other hand, Brun et al. analyzed a total of 308 patients and reported that the 5-year survival rate of 31 patients aged ≥75 years was 42% and that age was a significant prognostic factor. However, they also reported that the survival of those over 75 years was not different from that of the rest of the population [23]. Although the median follow-up of our study was shorter and the number of cases is currently smaller, our observed survival rates are reasonable compared with previous reports. Our results also indicate that the clinical stage might have prognostic value in determining survival outcomes, but age did not have prognostic value in such an elderly population. Interestingly, the DSS rate of patients aged >80 years was 100%. Whether “slow oncological progression” was associated with this result is unclear because of the small number of patients and the short follow-up period. Therefore, this result cannot be used as evidence for a more limited treatment choice at present. However, RRT alone should be the first choice for patients >80 years old. The survival rates of the patients with high KPS scores (>70) were better than those with low KPS scores (≤70), but the difference was not significant. KPS was not a significant prognostic factor in this preliminary result, but it may have a large impact on long-term survival. To evaluate survival outcomes accurately and verify prognostic factors such as clinical stage, age, and KPS, more cases need to be analyzed, a longer follow-up period is needed, and the results need to be compared with those of a younger population. Finally, the most appropriate treatment choice for elderly patients should be established.
Both acute and late toxicity should be evaluated carefully to establish a safe modality that achieves better survival outcomes and preserves the quality of life of elderly patients with cervical cancer. Lindegaard et al. reported that treatment was completed as planned in 68% of cases, delayed in 29% of cases, and stopped prematurely in 3% of cases. They concluded that elderly patients with cervical cancer in otherwise good health may tolerate radical radiotherapy with acceptable toxicity and reasonable survival rates [28]. In our study, 38 of 40 (95%) patients completed the treatment as planned; 1 (2.5%) completed after a delay and 1 (2.5%) could not complete the treatment. The two patients who experienced delay or cancellation of the treatment had KPS scores <50 and had RRT performed, but they could not receive HDR-BT. This result also indicates that elderly patients in good health can tolerate RRT (EBRT combined with HDR-ICBT). However, those with a poor performance status should be treated carefully; in some instances, a less invasive RRT (EBRT alone) must be chosen. For elderly patients in good health, tolerance for more aggressive treatment modalities such as RRT with CCT or S + ART with or without CCT should be discussed carefully. In our study, 8 patients with KPS scores >70 were treated with these more aggressive modalities (RRT with CCT: 3, S + ART: 3, S + ART with CCT: 2). As described above, the indications for the use of these aggressive modalities involved age, KPS, FIGO stage, and pathological risk factors. Regarding the patients treated with RRT with CCT, all of them were <80 years old and had KPS scores >70. Two of them were FIGO IIB and the remaining one was IIIB. Regarding the patients treated with S + ART with or without CCT, 4 were 75, and 1 was 76 years old. All of them had KPS scores >70 and had stage II disease (IIA: 2, IIB: 3). Adjuvant CCT has been performed on patients with postoperative KPS scores >70 and multiple pathological risk factors (at least 3) since 2008. As a result, two were treated with S + ART with CCT. One had wide parametrium invasion and both vascular and lymphatic invasion. The other had a large tumor (>4 cm), parametrium invasion, vascular invasion, and a positive vaginal surgical margin. Although nodal metastasis was the most important prognostic factor, two patients who had pathological nodal metastasis did not receive adjuvant CCT. This was because one had postoperative KPS score = 50, whereas the other was one of the oldest patient treated in 2000 and adjuvant CCT was not performed for elderly patients at that time. Therefore, they were treated with S + ART without CCT. All of the patients treated with these aggressive modalities completed the treatment without delay, but three of them (37.5%) experienced Grade 3 acute toxicity during and soon after the completion of RT. These results indicate that these aggressive modalities are not always safe in terms of acute toxicity. As for late toxicity, although the median follow-up was shorter, Grade 3 late toxicity was experienced by 2 of 40 (5%) patients, and no Grade 4 or higher late toxicity was experienced in our study. Several authors reported that the occurrence rates of Grade 3 or greater late morbidities were less than approximately 10%, and our results are compatible with those of previous reports [12, 13, 28, 29]. However, we should emphasize that Grade 3 late toxicity was only experienced in patients treated with the more aggressive modalities (RRT with CCT: 1, S + ART: 1). Aggressive modalities may be tolerable for patients with a good performance status, but they can easily cause severe acute or late toxicity compared with RRT alone. Considering these results, when aggressive treatment modalities are performed in elderly patients, management of both acute and late toxicity is very important to avoid delay or cancellation and to maintain quality of life. The finding that patients with KPS scores >70 can tolerate aggressive modalities with appropriate management, whereas those with KPS scores <50 may not tolerate even RRT alone, is also very important. KPS should be considered as one of the determinants in selecting a treatment modality for elderly patients.
In conclusion, the number of elderly patients with cervical cancer is increasing, and RRT provides good survival outcomes with acceptable toxicity. However, indications for the use of more aggressive modalities should be assessed carefully, even for patients who are in quite good health. Therefore, to establish appropriate treatment strategies, including combinations of RT with less invasive surgery and/or chemotherapy, larger studies and prospective studies should be performed. Finally, better survival outcomes and preservation of the quality of life may be achievable for the growing elderly population.
Notes
Conflict of interest
We declare that we have no conflict of interest.
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References
- 1.Abridged life tables for Japan 2008, Ministry of Health, Labour and Welfare. http://www.mhlw.go.jp/english/database/db-hw/vs02.html
- 2.Schwartz S (2009) Young cervical cancer patients and fertility. Semin Oncol Nurs 25:259–267PubMedCrossRefGoogle Scholar
- 3.Yang L, Fujimoto J, Qiu D, Sakamoto N (2009) Trends in cancer mortality in Japanese adolescents and young adults aged 15–29 years, 1970–2006. Ann Oncol 20:758–766PubMedCrossRefGoogle Scholar
- 4.Kokawa K, Takekida S, Kamiura S, Kita M, Enomoto T, Kawaguchi R, Saito J, Horie A, Umesaki N (2010) The incidence, treatment and prognosis of cervical carcinoma in young women: a retrospective analysis of 4, 975 cases in Japan. Eur J Gynaecol Oncol 31:37–43PubMedGoogle Scholar
- 5.Landoni F, Maneo A, Colombo A, Placa F, Milani R, Perego P, Favini G, Ferri L, Mangioni C (1997) Randomised study of radical surgery versus radiotherapy for stage Ib-IIa cervical cancer. Lancet 350:535–540PubMedCrossRefGoogle Scholar
- 6.Perez CA, Grigsby PW, Camel HM, Galakatos AE, Mutch D, Lockett MA (1995) Irradiation alone or combined with surgery in stage IB, IIA, and IIB carcinoma of uterine cervix: update of a nonrandomized comparison. Int J Radiat Oncol Biol Phys 31:703–716PubMedCrossRefGoogle Scholar
- 7.Gaze MN, Kelly CG, Dunlop PR, Redpath AT, Kerr GR, Cowie VJ (1992) Stage IB cervical carcinoma: a clinical audit. Br J Radiol 65:1018–1024PubMedCrossRefGoogle Scholar
- 8.Yamashita H, Nakagawa K, Tago M, Shiraishi K, Nakamura N, Ohtomo K, Oda K, Nakagawa S, Yasugi T, Taketani Y (2005) Comparison between conventional surgery and radiotherapy for FIGO stage I-II cervical carcinoma: a retrospective Japanese study. Gynecol Oncol 97:834–839PubMedCrossRefGoogle Scholar
- 9.Undurraga M, Loubeyre P, Dubuisson JB, Schneider D, Petignat P (2010) Early-stage cervical cancer: is surgery better than radiotherapy? Expert Rev Anticancer Ther 10:451–460 (Review)PubMedCrossRefGoogle Scholar
- 10.Korfage IJ, Essink-Bot ML, Mols F, van de Poll-Franse L, Kruitwagen R, van Ballegooijen M (2009) Health-related quality of life in cervical cancer survivors: a population-based survey. Int J Radiat Oncol Biol Phys 73:1501–1509PubMedCrossRefGoogle Scholar
- 11.Frumovitz M, Sun CC, Schover LR, Munsell MF, Jhingran A, Wharton JT, Eifel P, Bevers TB, Levenback CF, Gershenson DM, Bodurka DC (2005) Quality of life and sexual functioning in cervical cancer survivors. J Clin Oncol 23:7428–7436PubMedCrossRefGoogle Scholar
- 12.Sakurai H, Mitsuhashi N, Takahashi M, Yamakawa M, Akimoto T, Hayakawa K, Niibe H (2000) Radiation therapy for elderly patient with squamous cell carcinoma of the cervix. Gynecol Oncol 77:116–120PubMedCrossRefGoogle Scholar
- 13.Ikushima H, Takegawa Y, Osaki K, Furutani S, Yamashita K, Kawanaka T, Kubo A, Kudoh T, Nishitani H (2007) Radiation therapy for cervical cancer in the elderly. Gynecol Oncol 107:339–343PubMedCrossRefGoogle Scholar
- 14.Creasman WT (1995) New gynecologic cancer staging. Gynecol Oncol 58:157–158PubMedCrossRefGoogle Scholar
- 15.International Commission on Radiation Units and Measurements (1985) Dose and volume specification for intracavity therapy in gynecology. ICRU report 38. ICRU, WashingtonGoogle Scholar
- 16.Common Toxicity Criteria version 4.0 Japanese Translation—JCOG (2009) Japan Clinical Oncology GroupGoogle Scholar
- 17.Terret C, Albrand G, Droz JP (2004) Management and geriatric assessment of cancer in the elderly. Clin Prostate Cancer 2:236–240PubMedGoogle Scholar
- 18.Sekine I, Yamamoto N, Kunitoh H, Ohe Y, Tamura T, Kodama T, Saijo N (2004) Treatment of small cell lung cancer in the elderly based on a critical literature review of clinical trials. Cancer Treat Rev 30:359–368PubMedCrossRefGoogle Scholar
- 19.Harlacher R, Füsgen I (2000) Geriatric assessment in the elderly cancer patient. J Cancer Res Clin Oncol 126:369–374PubMedCrossRefGoogle Scholar
- 20.Yancik R, Havlik RJ, Wesley MN, Ries L, Long S, Rossi WK, Edwards BK (1996) Cancer and comorbidity in older patients: a descriptive profile. Ann Epidemiol 6:399–412PubMedCrossRefGoogle Scholar
- 21.Hurria A, Wong FL, Villaluna D, Bhatia S, Chung CT, Mortimer J, Hurvitz S, Naeim A (2008) Role of age and health in treatment recommendations for older adults with breast cancer: the perspective of oncologists and primary care providers. J Clin Oncol 26:5386–5392PubMedCrossRefGoogle Scholar
- 22.Mitchell PA, Waggoner S, Rotmensch J, Mundt AJ (1998) Cervical cancer in the elderly treated with radiation therapy. Gynecol Oncol 71:291–298PubMedCrossRefGoogle Scholar
- 23.Brun JL, Stoven-Camou D, Trouette R, Lopez M, Chene G, Hocké C (2003) Survival and prognosis of women with invasive cervical cancer according to age. Gynecol Oncol 91:395–401PubMedCrossRefGoogle Scholar
- 24.Wright JD, Gibb RK, Geevarghese S, Powell MA, Herzog TJ, Mutch DG, Grigsby PW, Gao F, Trinkaus KM, Rader JS (2005) Cervical carcinoma in the elderly: an analysis of patterns of care and outcome. Cancer 103:85–91PubMedCrossRefGoogle Scholar
- 25.de Rijke JM, van der Putten HW, Lutgens LC, Voogd AC, Kruitwagen RF, van Dijck JA, Schouten LJ (2002) Age-specific differences in treatment and survival of patients with cervical cancer in the southeast of The Netherlands, 1986–1996. Eur J Cancer 38:2041–2047PubMedGoogle Scholar
- 26.Chen SW, Liang JA, Yang SN, Lin FJ (2003) High dose-rate brachytherapy for elderly patients with uterine cervical cancer. Jpn J Clin Oncol 33:221–228PubMedCrossRefGoogle Scholar
- 27.Mitsuhashi N, Takahashi M, Nozaki M, Yamakawa M, Takahashi T, Sakurai H, Maebayashi K, Hayakawa K, Niibe H (1995) Squamous cell carcinoma of the uterine cervix: radiation therapy for patients aged 70 years and older. Radiology 194:141–145PubMedGoogle Scholar
- 28.Lindegaard JC, Thranov IR, Endelholm SA (2000) Radiotherapy in the management of cervical cancer in elderly patients. Radiother Oncol 56:9–15PubMedCrossRefGoogle Scholar
- 29.Magné N, Mancy NC, Chajon E, Duvillard P, Pautier P, Castaigne D, Lhommé C, Morice P, Haie-Meder C (2009) Patterns of care and outcome in elderly cervical cancer patients: a special focus on brachytherapy. Radiother Oncol 91:197–201PubMedCrossRefGoogle Scholar