Carbon ion radiotherapy for elderly patients 80 years and older with stage I non-small cell lung cancer

doi:10.1016/j.lungcan.2008.07.007

Lung Cancer

Volume 64, Issue 1, April 2009, Pages 45-50

https://doi.org/10.1016/j.lungcan.2008.07.007 Get rights and content

Abstract

Surgical resection is the standard treatment for stage I non-small cell lung cancer (NSCLC). However, elderly patients with NSCLC often suffer from other conditions, such as chronic obstructive pulmonary disease (COPD) or cardiovascular disease, and are not suitable candidates for surgery. Different modalities to treat stage I NSCLC have been developed, such as stereotactic radiotherapy (SRT), proton beam radiotherapy and carbon ion radiotherapy (CIRT). Between April 1999 and November 2003, we treated 129 patients with stage I NSCLC using CIRT. In this study, we focused on 28 patients aged 80 years and older who underwent CIRT, and analyzed the effectiveness of CIRT in treating their lung cancer and the impact on their activity of daily life (ADL). The 5-year local control rate for these patients was 95.8%, and the 5-year overall survival rate was 30.7%, but there were no patients who started home oxygen therapy or had decreased ADL. Our data demonstrate that CIRT was effective in treating elderly patients with stage I NSCLC.

Introduction

The World Health Organization has estimated that in 2004 there were 32.5 million people aged 60 years and older living in Japan, and that this number represented 25.6% of the population. At that time, the number of deaths per 100,000 people due to lung cancer was 71.3 for men and 24.8 for women, making lung cancer first among men and second among women as a cause of death [1], [2]. In the United States, about 80% of patients with lung cancer are over the age of 60, and about 22% are over the age of 80 [3].

In light of the explosion in the incidence of lung cancer in elderly people, there is a growing need for safe and effective treatments. Surgical resection has maintained a stubborn hold as the treatment for stage I non-small cell lung cancer (NSCLC) [4]. However, elderly patients who often suffer from other conditions, such as chronic obstructive pulmonary disease (COPD), cardiovascular disease, or other cancers, are not good candidates for surgery. In our hospital, we have used carbon ion radiotherapy (CIRT) for medically inoperable stage I NSCLC since 1994. Carbon ion beams have the physical advantage of delivering a highly precise dose concentration and having a high rate of biological effectiveness [5]. As we previously reported, through the prudent use of CIRT, we have been able to take full advantage of its unique and valuable characteristics for the treatment of stage I NSCLC. We have achieved high local control with low complication rates. In those clinical studies, all 129 patients with stage I NSCLC were able to complete CIRT. Median age of the patients was 75 years (range 47–88 years) and 106 patients were not eligible for surgery. The 5-year overall survival and local control rates for all patients were 43.4% and 91.7%, respectively. For patients with T2 disease, the 5-year local control rate was 84.7% [6], [7].

In this study, we evaluated the efficacy and toxicity of CIRT for stage I NSCLC, with a focus on elderly patients 80 years and older.

Section snippets

Patients and methods

Between April 1999 and November 2003, 129 patients with stage I NSCLC lung cancer were treated using CIRT at the National Institute of Radiological Sciences (NIRS) in Chiba, Japan. All patients were enrolled in a phase II study of CIRT for stage I NSCLC. Eligibility was based on histological evidence for the peripheral type of stage I NSCLC. All of the patients had a performance status (PS) score between 0 and 2 according to the World Health Organization guidelines, but the patient's age was

Survival and tumor control

The 2-year and 5-year local control rates were both 95.8% for the 29 lesions in the 28 elderly patients (Fig. 1). Only 1 patient with T2 disease who had a tumor that was 42 mm in size had local recurrence inside the radiation field 12 months after CIRT. In patients with T2 disease, the 2-year and 5-year local control rates were both 91.7%, and in patients with T1 disease they were 100% (Fig. 2). For tumors greater than 4 cm in size, the 5-year local control rate was 80.0%. In 10 patients without

Discussion

Surgical resection is the standard treatment for stage I NSCLC, with a 5-year overall survival rate of approximately 60–70% [18], [19], and a 5-year local control rate exceeding 80% [20]. When elderly patients with NSCLC who were able to be candidates for surgery were compared to younger patients, no differences in the 5-year overall survival rate by surgical resection were reported in some papers [4], [21], [22]. There were no significant differences reported in the rates of all complications,

Conclusions

In this study, the eligibility criteria were restricted to medically inoperable cases, and the general conditions of our cases were inferior to those for surgical cases. Considering these unfavorable conditions, carbon ion radiotherapy was successfully used and provided safe and effective results for elderly patients 80 years and older with stage I NSCLC. The use of CIRT is not widespread in the world but it has a significant potential for the control of lung cancer. For a thorough evaluation

Conflict of interest statement

None.

Acknowledgements

This work was supported by the Research Project with Heavy Ions at NIRS-HIMAC, JSPS KAKENHI (18591398) and a Grant-in-Aid for Cancer Research (19-06) from the Ministry of Health, Labour and Welfare. We are grateful to Ms. Hiroko Saitou (Research Center Hospital for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan), Dr. Tomoyasu Yashiro (Department of Thoracic Surgery, Nissan Tamagawa Hospital, Tokyo, Japan), Dr. Kenji Kagei (Department of Radiology, Kushiro

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Cited by (42)

Value of carbon-ion radiotherapy for early stage non-small cell lung cancer
2022, Clinical and Translational Radiation Oncology
Citation Excerpt :
In conclusion, it seems clear that CIRT does not aggravate the occurrence of RP after radiotherapy with carbon ion beam in NSCLC patients, and its incidence is sometimes even lower than that recorded after SBRT [8,10,28,55,56]. Many oncologists of radiation therapy regard CIRT as safe and effective despite combined interstitial lung disease and old age (Table 1) [8,30,32,36,37,49,54,57,58]. Compared to conventional photon external beam radiation, carbon ion radiotherapy has a superior dose distribution.
Carbon-ion radiotherapy (CIRT) is an important part of modern radiotherapy. Compared to conventional photon radiotherapy modalities, CIRT brings two major types of advantages to physical and biological aspects respectively. The physical advantages include a substantial dose delivery to the tumoral area and a minimization of dose damage to the surrounding tissue. The biological advantages include an increase in double-strand breaks (DSBs) in DNA structures, an upturn in oxygen enhancement ratio and an improvement of radiosensitivity compared with X-ray radiotherapy. The two advantages of CIRT are that the therapy not only inflicts major cytotoxic lesions on tumor cells, but it also protects the surrounding tissue. According to annual diagnoses, lung cancer is the second most common cancer worldwide, followed by breast cancer. However, lung cancer is the leading cause of cancer death. Patients with stage I non-small cell lung cancer (NSCLC) who are optimally received the treatment of lobectomy. Some patients with comorbidities or combined cardiopulmonary insufficiency have been shown to be unable to tolerate the treatment when combined with surgery. Consequentially, radiotherapy may be the best treatment option for this patient category. Multiple radiotherapy options are available for these cases, such as stereotactic body radiotherapy (SBRT), volumetric modulated arc therapy (VMAT), and intensity-modulated radiotherapy (IMRT). Although these treatments have brought some clinical benefits to some patients, the resulting adverse events (AEs), which include cardiotoxicity and radiation pneumonia, cannot be ignored. The damage and toxicity to normal tissue also limit the increase of tumor dose. Due to the significant physical and biological advantages brought by CIRT, some toxicity induced by radiotherapy may be avoided with CIRT Bragg Peak. CIRT brought clinical benefits to lung cancer patients, especially geriatric patients. This review introduced the clinical efficacy and research results for non-small cell lung cancer (NSCLC) with CIRT.
Determining RBE for development of lung fibrosis induced by fractionated irradiation with carbon ions utilizing fibrosis index and high-LET BED model
2019, Clinical and Translational Radiation Oncology
Carbon ion radiotherapy (CIRT) with raster scanning technology is a promising treatment for lung cancer and thoracic malignancies. Determining normal tissue tolerance of organs at risk is of utmost importance for the success of CIRT. Here we report the relative biological effectiveness (RBE) of CIRT as a function of dose and fractionation for development of pulmonary fibrosis using well established fibrosis index (FI) model.
Dose series of fractionated clinical quality CIRT versus conventional photon irradiation to the whole thorax were compared in C57BL6 mice. Quantitative assessment of pulmonary fibrosis was performed by applying the FI to computed tomography (CT) data acquired 24-weeks post irradiation. RBE was calculated as the ratio of photon to CIRT dose required for the same level of FI. Further RBE predictions were performed using the derived equation from high-linear energy transfer biologically effective dose (high-LET BED) model.
The averaged lung fibrosis RBE of 5-fraction CIRT schedule was determined as 2.75 ± 0.55. The RBE estimate at the half maximum effective dose (RBE_ED50) was estimated at 2.82 for clinically relevant fractional sizes of 1–6 Gy. At the same dose range, an RBE value of 2.81 ± 0.40 was predicted by the high-LET BED model. The converted biologically effective dose (BED) of CIRT for induction of half maximum FI (BED_ED50) was identified to be 58.12 Gy_3.95. In accordance, an estimated RBE of 2.88 was obtained at the BED_ED50 level. The LQ model radiosensitivity parameters for 5-fraction was obtained as α_H = 0.3030 ± 0.0037 Gy⁻¹ and β_H = 0.0056 ± 0.0007 Gy⁻².
This is the first report of RBE estimation for CIRT with the endpoint of pulmonary fibrosis in-vivo. We proposed in present study a novel way to mathematically modeling RBE by integrating RBE_max and α/β_L based on conventional high-LET BED conception. This model well predicted RBE in the clinically relevant dose range but is sensitive to the uncertainties of α/β estimates from the reference photon irradiation (α/β_L). These findings will assist to eliminate current uncertainties in prediction of CIRT induced normal tissue complications and builds a solid foundation for development of more accurate in-vivo data driven RBE estimates.
A Dose Escalation Clinical Trial of Single-Fraction Carbon Ion Radiotherapy for Peripheral Stage I Non–Small Cell Lung Cancer
2017, Journal of Thoracic Oncology
Our objective was to report initial results of a dose escalation trial of single-fraction carbon ion radiotherapy for peripheral stage I NSCLC.
Between April 2003 and February 2012, a total of 218 patients were treated. The total dose was raised from 28 to 50 Gy (relative biological effectiveness [RBE]). There were 157 male and 61 female patients, with a median age of 75 years. Of the tumors, 123 were stage T1 and 95 were stage T2. A total of 134 patients (61.5%) were medically inoperable. By histological type, there were 146 adenocarcinomas, 68 squamous cell carcinomas, three large cell carcinomas, and one mucoepidermoid carcinoma.
The median follow-up was 57.8 months (range 1.6–160.7). The overall survival rate at 5 years was 49.4%. The local control (LC) rate was 72.7%. A statistically significant difference in LC rate (p = 0.0001, log-rank test) was seen between patients receiving 36 Gy (RBE) or more and those receiving less than 36 Gy (RBE). In 20 patients irradiated with 48 to 50 Gy (RBE), the LC rate at 5 years was 95.0%, the overall survival rate was 69.2%, and the progression-free survival rate was 60.0% (median follow-up was 58.6 months). With dose escalation, LC tended to improve. As for adverse lung and skin reactions, there were no patients with grade 3 or higher reactions, and less than 2% had a grade 2 reaction. Regarding chest wall pain, only one patient had grade 3 late toxicity.
We have reported the outcome of a dose escalation study of single-fraction carbon ion radiotherapy for stage I NSCLC, showing the feasibility of obtaining excellent results comparable to those with previous fractionated regimens.
Non-small cell lung cancer irradiation in elderly
2016, Cancer/Radiotherapie
Les personnes âgées de plus de 65 ans sont souvent exclues des essais cliniques en cancérologie. Cependant, plus de la moitié des patients atteints d’un carcinome bronchique non à petites cellules ont plus de 65 ans. Toute stratégie thérapeutique doit être décidée en réunion de concertation pluridisciplinaire après une évaluation gériatrique adaptée. Les patients dont le score au questionnaire de dépistage G8 est inférieur ou égal à 14 doivent bénéficier de l’évaluation approfondie oncogériatrique de Balducci et Extermann. Lorsqu’il existe une indication de radiothérapie thoracique, l’âge n’est pas une contre-indication en soi. La radiothérapie stéréotaxique doit être l’alternative à la chirurgie pour les cancers pulmonaires localisés chez les patients âgés inopérables médicalement ou refusant la chirurgie car elle permet un allongement significatif de la survie globale. Pour les formes évoluées, une chimioradiothérapie le plus souvent séquentielle, rarement concomitante, peut être proposée aux sujets âgés en bon état général. Pour les autres, une radiothérapie exclusive palliative, une chimiothérapie par un ou deux produits, une biothérapie ou uniquement des soins de supports peuvent être discutés.
People over the age of 65 are often excluded from participation in oncological clinical trials. However, more than half of patients diagnosed with non-small-cell lung cancer are older than 65 years. Any therapeutic strategy must be discussed in multidisciplinary meetings after adapted geriatric assessment. Patients who benefit from the comprehensive geriatric assessment (CGA) of Balducci and Extermann are those whose G8 screening tool score is less than or equal to 14. Age itself does not contraindicate a curative therapeutic approach. Stereotactic radiotherapy is an alternative to surgery for early stages in elderly patients who are medically inoperable or who refuse surgery, because it significantly increases overall survival. Mostly sequential (rarely concomitant) chemoradiotherapy can be proposed to elderly patients with locally advanced stages in good general state of health. For the others, an exclusive palliative radiotherapy, a single or dual agent of chemotherapy, a targeted drug or best supportive care only may be discussed.
Single-Fraction Carbon-Ion Radiation Therapy for Patients 80 Years of Age and Older with Stage i Non-Small Cell Lung Cancer
2016, International Journal of Radiation Oncology Biology Physics
Citation Excerpt :
Table 3 shows the patients’ average values according to the criteria of stage II chronic obstructive pulmonary disease (COPD), both before and after CIRT. The tendency of pulmonary function was similar to that reported by Sugane et al (16), although a statistical comparison was not performed. Among patients with low pulmonary function, the differences between the items shown in Table 3 before and after CIRT were significantly greater than those of the patients with non-low pulmonary function.
In an aging society, many senior citizens want less invasive treatment because of potential medical complications. The National Institute of Radiological Sciences has started to treat stage I lung cancer with single-fraction carbon-ion radiation therapy (CIRT) as a dose escalation prospective phase 1/2 trial. We evaluated the efficacy and safety of CIRT for patients 80 years of age and older, undergoing single-fraction CIRT.
Peripheral non-small cell lung cancer patients who were treated with single-fraction CIRT were prospectively followed. We analyzed the data from among these patients 80 years of age and older.
There were 70 patients. Median age was 83 years (range: 80-89) and median follow-up period was 42.7 months (range: 12-128 months). Three-year local control, cause-specific survival, and overall survival rates were 88.0%, 81.6%, and 72.4%, respectively. Five-year local control, cause-specific survival, and overall survival rates were 85.8%, 64.9%, and 39.7%, respectively. There were no adverse effects higher than grade 2 either in the acute or late phase in terms of skin and lung. Analgesic agents were necessary for only 5 patients (7.1%), to relieve muscular or rib fracture pain caused by irradiation.
Single-fraction CIRT was low-risk and effective, even for the elderly.
New techniques and potential benefits for radiotherapy of lung cancer
2014, Cancer/Radiotherapie
La radiothérapie est utilisée dans les cancers du poumon inopérables, associée ou non à de la chimiothérapie. La radiothérapie classique donne des résultats décevants. De nouvelles techniques permettent une meilleure adaptation au volume tumoral et limitent l’irradiation des tissus sains avec, à terme, la possibilité d’augmenter les doses dans la tumeur et potentiellement d’améliorer la probabilité de survie. Avec la radiothérapie conformationnelle par modulation d’intensité, il est possible de conformer les isodoses à des volumes complexes. Elle est largement utilisée et semble indiquée quand la tumeur est localement évoluée. Ses gains dosimétriques sont démontrés mais les résultats cliniques sont encore hétérogènes. La radiothérapie stéréotaxique permet le traitement de petits volumes cibles par de multiples faisceaux étroits. Elle nécessite des appareils dédiés ou des équipements adaptés sur des accélérateurs classiques. Pour les tumeurs de faible stade, son efficacité est comparable à la chirurgie avec une toxicité acceptable. La curiethérapie endobronchique peut aussi être utilisée pour des tumeurs de faible stade répondant à des critères particuliers. L’hadronthérapie est une technique encore expérimentale. Les hadrons possèdent des propriétés physiques permettant une distribution de dose très précise. Dans les rares études publiées, la toxicité est globalement inférieure aux autres techniques mais pour les tumeurs de faible stade, son efficacité ne semblerait pas supérieure celle de la radiothérapie en conditions stéréotaxiques. Ces techniques sont optimisées par l’imagerie métabolique qui permet de mieux définir la cible et d’évaluer la réponse thérapeutique, la radiothérapie guidée par l’image qui permet un repositionnement plus précis et par les techniques d’asservissement respiratoire qui prennent en compte des mouvements de la cible.
Radiotherapy is used for inoperable lung cancers, sometimes in association with chemotherapy. Outcomes of conventional radiotherapy are disappointing. New techniques improve adaptation to tumour volume, decrease normal tissue irradiation and lead to increasing tumour dose with the opportunity for improved survival. With intensity-modulated radiation therapy, isodoses can conform to complex volumes. It is widely used and seems to be indicated in locally advanced stages. Its dosimetric improvements have been demonstrated but outcomes are still heterogeneous. Stereotactic radiotherapy allows treatment of small volumes with many narrow beams. Dedicated devices or appropriate equipment on classical devices are needed. In early stages, its efficacy is comparable to surgery with an acceptable toxicity. Endobronchial brachytherapy could be used for early stages with specific criteria. Hadrontherapy is still experimental regarding lung cancer. Hadrons have physical properties leading to very accurate dose distribution. In the rare published studies, toxicities are roughly lower than others techniques but for early stages its effectiveness is not better than stereotactic radiotherapy. These techniques are optimized by metabolic imaging which precisely defines the target volume and assesses the therapeutic response; image-guided radiation therapy which allows a more accurate patient set up and by respiratory tracking or gating which takes account of tumour respiratory motions.

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Carbon ion radiotherapy for elderly patients 80 years and older with stage I non-small cell lung cancer

Abstract

Introduction

Section snippets

Patients and methods

Survival and tumor control

Discussion

Conclusions

Conflict of interest statement

Acknowledgements

Int J Radiat Oncol Biol Phys

J Thorac Oncol

Chest

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Radiother Oncol

Int J Radiat Oncol Biol Phys

Chest

Chest

Chest

Chest

Thorac Surg Clin

Int J Radiat Oncol Biol Phys

Chest

Int J Radiat Oncol Biol Phys