The deep inspiration breath-hold technique in the treatment of inoperable non–small-cell lung cancer

doi:10.1016/S0360-3016(00)00583-6

International Journal of Radiation OncologyBiologyPhysics

Volume 48, Issue 1, 1 August 2000, Pages 81-87

https://doi.org/10.1016/S0360-3016(00)00583-6 Get rights and content

Abstract

Purpose: Conventional radiotherapeutic techniques are associated with lung toxicity that limits the treatment dose. Motion of the tumor during treatment requires the use of large safety margins that affect the feasibility of treatment. To address the control of tumor motion and decrease the volume of normal lung irradiated, we investigated the use of three-dimensional conformal radiation therapy (3D-CRT) in conjunction with the deep inspiration breath-hold (DIBH) technique.

Methods and Materials: In the DIBH technique, the patient is initially maintained at quiet tidal breathing, followed by a deep inspiration, a deep expiration, a second deep inspiration, and breath-hold. At this point the patient is at approximately 100% vital capacity, and simulation, verification, and treatment take place during this phase of breath-holding.

Results: Seven patients have received a total of 164 treatment sessions and have tolerated the technique well. The estimated normal tissue complication probabilities decreased in all patients at their prescribed dose when compared to free breathing. The dose to which patients could be treated with DIBH increased on average from 69.4 Gy to 87.9 Gy, without increasing the risk of toxicity

Conclusions: The DIBH technique provides an advantage to conventional free-breathing treatment by decreasing lung density, reducing normal safety margins, and enabling more accurate treatment. These improvements contribute to the effective exclusion of normal lung tissue from the high-dose region and permit the use of higher treatment doses without increased risks of toxicity.

Introduction

The limited ability to eradicate intrathoracic tumors with conventional radiotherapeutic approaches represents a vexing shortcoming in the treatment of inoperable non–small cell lung cancer (NSCLC). When patients receiving 65 Gy with or without chemotherapy were carefully evaluated for local tumor control, only 17% and 15%, respectively, were free of disease after treatment (1). There are several possible reasons for the failure to control NSCLC locally with radiation. Radiation resistance to the dose levels classically used perhaps represents the major contributing factor to the high incidence of local failure. However, while higher doses appear to be required for improved local control (2), the volume of lung in the high-dose region has limited the ability to escalate the dose with conventional techniques.

Three-dimensional conformal radiation therapy (3D-CRT) represents an approach to improve the local outcome of radiotherapy in NSCLC 3, 4. The major aim of this method is to decrease the risk of underdosing or missing portions of the tumor. In addition, due to the improved ability to conform the high radiation dose to the target, considerable amounts of normal lung, esophagus, and heart can be effectively excluded from the high radiation dose regions. This provides a potential for increasing the tumor dose to levels beyond those feasible with conventional radiotherapy with a concomitant decrease in the normal tissue complication probability (NTCP). Single-institution and cooperative group studies of dose escalation are currently underway 5, 6, 7 to evaluate the efficacy of this strategy.

Motion of the tumor and of the lung itself during the delivery of each treatment appears to affect the outcome of radiotherapy in inoperable NSCLC. Lung tumors have been shown to move substantially during quiet breathing, causing inaccuracies in treatment delivery 8, 9. Underdosage of the clinical target volume (CTV) may result if the tumor target moves outside of the treatment volume during the administration of radiotherapy. To compensate for this motion, a large margin is usually used, consequently increasing the amount of normal lung tissue in the high-dose volume and limiting the amount of radiation that can be delivered. Thus, 3D-CRT NSCLC dose-escalation studies require approaches to reduce the intrafraction organ motion and the volume of lung receiving radiation.

Two distinct techniques have been used to reduce the effect of respiratory motion. The first involves confining the radiation delivery to a specified phase in the breathing cycle by gating the linear accelerator while the patient breathes freely. Breathing is monitored with devices that trigger radiation delivery during specific phases of the patient’s respiratory cycle (10). In the second approach, breathing is controlled either voluntarily by the patient or by using an occlusion valve (11). The use of gated treatments has been evaluated 10, 12, 13, 14 and offers the advantage of allowing patients to breathe freely while the radiation beam is turned on and off.

One method to regulate breathing is active breathing control (ABC) developed by Wong et al. 11, 15 This technique has been explored as a possible treatment for a variety of tumors. It has been shown to be a reproducible method of controlling patient breathing through the use of an occlusion valve at a specified level in the respiratory cycle.

The most extensively explored control technique is the deep inspiration breath-hold (DIBH) technique. The DIBH technique involves coaching the patient to the same reproducible deep inspiration level during simulation, radiation treatments, and port film verification. This approach utilizes a modified slow vital capacity maneuver (16), which is highly reproducible, a necessity for fractionated radiation therapy.

The feasibility of the DIBH technique was studied by Hanley et al. (17) An intrabreath-hold reproducibility of 1.0 ± 0.9 mm and interbreath-hold reproducibility of 2.5 ± 1.6 mm was found as determined by diaphragm position. Further, the DIBH approach reduced the mass of lung irradiated to high doses compared to conventional free breathing and gated techniques. On average, gated treatment reduced the mass of lung receiving greater than 25 Gy by approximately one-fifth relative to free breathing, whereas DIBH reduced the mass by one-third. Patients were able to comfortably carry out 10–13 breath-holds in one session, with breath-hold duration of 12 to 16 seconds. It was concluded that with the DIBH technique the potential for dose escalation was significantly improved because less normal lung was irradiated to high dose.

Based on the findings of our feasibility study, the DIBH technique was implemented at the Memorial Sloan-Kettering Cancer Center (MSKCC) for the treatment of patients with NSCLC entered into our 3D-CRT dose-escalation study 6, 18, 19. This report describes our preliminary clinical experience with this approach.

Section snippets

DIBH technique

The DIBH technique required special procedures in patient training, simulation, verification, and treatment. In the DIBH maneuver, the patient was initially brought to quiet tidal breathing. This was followed by verbally coaching the patient to perform a slow deep inspiration, a slow deep expiration, and a second slow deep inspiration and breath-hold (Fig. 1). The patient was at approximately 100% vital capacity during the breath-hold.

To monitor the lung inflation levels, patients breathed

Dosimetry

In Fig. 3, a comparison of treatment plans for free breathing and DIBH technique is presented for a patient receiving 81 Gy (Patient 1 in Fig. 4, Fig. 5. In Fig. 3A, the patient is presented at free breathing and a large portion of the patient’s lung volume is encompassed by the 50% isodose curve (green line). Also, note the artifact in the CT reconstruction of the diaphragm caused by respiration. In Fig. 3B, the patient is at deep inspiration. There is no diaphragmatic artifact and most of

Discussion

This study demonstrates the feasibility of the DIBH technique in the treatment of NSCLC. The use of DIBH was motivated by the recognition that higher doses of radiation can lead to improved local control 2, 7, 25, but that the development of radiation pneumonitis would be dose-limiting. Our current treatment policy for thoracic tumors limits the administered dose to a level not exceeding a NTCP of 25%. This policy has been effective in reducing pulmonary toxicity despite the increase of

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Cited by (358)

Deep inspirational breast hold (DIBH) for right breast irradiation: Improved sparing of liver and lung tissue
2024, Clinical and Translational Radiation Oncology
To reduce liver and lung dose during right breast irradiation while maintaining optimal dose to the target volume. This dose reduction has the potential to decrease acute side effects and long-term toxicity.
16 patients treated with radiation therapy for localized carcinoma of the right breast were included retrospectively. For the planning CT, each patient was immobilised on an indexed board with the arms placed above the head. CT scans were acquired in free-breathing (FB) as well as with deep inspiration breath hold (DIBH). Both scans were acquired with the same length. Planning target volumes (PTV's) were created with a 5 mm margin from the respective clinical target volumes (CTV's) on both CT datasets. The liver was outlined as scanned. Dose metrics evaluated were as follows: differences in PTV coverage, dose to the liver (max, mean, V90%, V50%, V30%), dose to lung (mean, V20Gy, relative electron density) and dose to heart (Dmax). The p-values were calculated using Wilcoxon signed-rank tests. A p-value was significant when <0.05.
Differences in PTV coverage between plans using FB and DIBH were less than 2 %. Maximum liver dose was significantly less using DIBH: 17.5 Gy versus FB: 40.3 Gy (p < 0.001). The volume of the liver receiving 10 % of the dose was significantly less using DIBH with 1.88 cm³ versus 72.2 cm³ under FB (p < 0.001). The absolute volume receiving 20 Gy in the right lung was larger using DIBH: 291 cm³ versus 230 cm³ under FB (p < 0.001) and the relative volume of lung receiving dose greater than 20 Gy was smaller with DIBH: 11.5 % versus 14 % in FB (p = 0.007). The relative electron density of lung was significantly less with DIBH: 0.59 versus 0.62 with FB, (p < 0.001). This suggests that the lung receives less dose due to its lower density when using DIBH.
Radiation of the right breast using DIBH spares liver and lung tissue significantly and thus carries the potential of best practice for right sided breast cancer.
DIBH reduces right coronary artery and lung radiation dose in right breast cancer loco-regional radiotherapy
2024, Medical Dosimetry
To determine whether deep inspiratory breath-hold (DIBH) reduces dose to organs-at-risk (OAR), in particular the right coronary artery (RCA), in women with breast cancer requiring right-sided post-mastectomy radiotherapy (PMRT) including internal mammary chain (+IMC) radiotherapy (RT).
Fourteen consecutive women requiring right-sided PMRT + IMC were retrospectively identified. Nodal delineation was in accordance with European Society for Radiology and Oncology (ESTRO) guidelines and tangential chest wall fields marked. Patients were planned with Anisotropic Analytical Algorithm using free-breathing (FB) and DIBH datasets. Dose was calculated using Acuros External Beam algorithm. FB and DIBH dose comparisons were analyzed for heart, RCA and right lung, as were chest wall and IMC planning target volumes (PTVs).
DIBH vs FB resulted in median decreases of: the RCA mean dose by 0.6Gray (Gy) (interquartile range (IQR) 0.1, 1.9) (p = 0.002), RCA max dose by 1.8Gy (IQR 0.8, 6.1) (p = 0.002), and V5Gy by 2.9% (IQR 0.0, 37.2) (p = 0.016). RCA data indicated no statistically significant dosimetric reduction ≥10Gy.
A median reduction of 1.7Gy (c -0.0, 7.1) (p = 0.019) in maximum heart dose was recorded with DIBH vs FB; no significant difference was observed in other heart and left anterior descending coronary artery parameters.
The median reduction in right lung mean dose was 2.8Gy for DIBH vs FB plans (IQR 1.6, 3.6) (p = 0.001); significant median reductions of V5Gy, V20Gy, and V30Gy were all achieved with DIBH.
Chest wall PTV coverage did not significantly differ between DIBH and FB plans; IMC dosimetric coverage improved with use of DIBH (V47.5Gy, V45Gy, V42Gy).
DIBH reduced OAR dose in right-sided PMRT + IMC patients. A novel finding was that DIBH decreased RCA dose. Heart and right lung dose were also decreased with DIBH, whilst optimally dosed PTVs were maintained.
Stereotactic body radiation therapy for sarcoma pulmonary metastases
2023, Radiotherapy and Oncology
Stereotactic body radiation therapy (SBRT) is standard for patients with inoperable early-stage NSCLC. We hypothesized that SBRT for sarcoma pulmonary metastases would achieve high rates of local control with acceptable toxicity and that patients with oligometastatic disease may achieve prolonged survival following SBRT.
This retrospective review included consecutive patients at our institution treated with SBRT for sarcoma pulmonary metastases. Cumulative incidence of local failure (LF) was estimated using a competing risks framework.
We identified 66 patients treated to 95 pulmonary metastases with SBRT. The median follow-up from the time of SBRT was 36 months (95% CI 34 – 53 months). The cumulative incidence of LF at 12 and 24 months was 3.1% (95% CI 0.9 – 10.6%) and 7.4% (95% CI 4.0% - 13.9%), respectively. The 12- and 24-month overall survival was 74% (95% CI 64 – 86%) and 49% (38 – 63%), respectively. Oligometastatic disease, intrathoracic only disease, and performance status were associated with improved survival on univariable analysis. Three patients had grade 2 pneumonitis, and one patient had grade 2 esophagitis. No patients had ≥ grade 3+ toxicities.
To the best of our knowledge, this is the largest series of patients treated with SBRT for pulmonary sarcoma metastases. We observed that SBRT offers an effective alternative to surgical resection with excellent local control and low proportions of toxicity.
ESTRO-ACROP guideline: Recommendations on implementation of breath-hold techniques in radiotherapy
2023, Radiotherapy and Oncology
The use of breath-hold techniques in radiotherapy, such as deep-inspiration breath hold, is increasing although guidelines for clinical implementation are lacking. In these recommendations, we aim to provide an overview of available technical solutions and guidance for best practice in the implementation phase. We will discuss specific challenges in different tumour sites including factors such as staff training and patient coaching, accuracy, and reproducibility. In addition, we aim to highlight the need for further research in specific patient groups. This report also reviews considerations for equipment, staff training and patient coaching, as well as image guidance for breath-hold treatments. Dedicated sections for specific indications, namely breast cancer, thoracic and abdominal tumours are also included.
Respiratory motion management for external radiotherapy treatment
2022, Cancer/Radiotherapie
We present the update of the recommendations of the French society of oncological radiotherapy on respiratory motion management for external radiotherapy treatment. Since twenty years and the report 62 of ICRU, motion management during the course of radiotherapy treatment has become an increasingly significant concern, particularly with the development of hypofractionated treatments under stereotactic conditions, using reduced safety margins. This article related orders of motion amplitudes for different organs as well as the definition of the margins in radiotherapy. An updated review of the various movement management strategies is presented as well as main technological solutions enabling them to be implemented: when acquiring anatomical data, during planning and when carrying out treatment. Finally, the management of these moving targets, such as it can be carried out in radiotherapy departments, will be detailed for a few concrete examples of localizations (abdominal, thoracic and hepatic).
Nous présentons la mise à jour des recommandations de la Société française de radiothérapie oncologique sur la gestion des mouvements respiratoires en radiothérapie. Depuis plus d’une vingtaine d’années et la publication du rapport 62 de l’International Commission on Radiation Units and Measurements (ICRU), la gestion des mouvements lors de traitement de radiothérapie est devenue une préoccupation de plus en plus prégnante notamment avec le développement des traitements hypofractionnés en conditions stéréotaxiques, utilisant des marges sécurité réduites. Cet article rappelle les ordres de grandeur des amplitudes de mouvement pour différents organes ainsi que la définition des marges en radiothérapie. Il propose ensuite une revue actualisée des différentes stratégies de gestion des mouvements et des principales solutions technologiques permettant de les mettre en œuvre: lors de l’acquisition des données anatomiques, lors de la planification et lors de la réalisation du traitement. Enfin, la prise en charge de ces cibles mobiles, telle qu’elle peut être réalisée dans des services de radiothérapie sera détaillée pour quelques exemples concrets de localisations (abdominales, thoraciques et hépatiques).
Mechanically-assisted and non-invasive ventilation for radiation therapy: A safe technique to regularize and modulate internal tumour motion
2019, Radiotherapy and Oncology
Current motion mitigation strategies, like margins, gating, and tracking, deal with geometrical uncertainties in the tumour position, induced by breathing during radiotherapy (RT). However, they often overlook motion variability in amplitude, respiratory rate, or baseline position, when breathing spontaneously. Consequently, this may negatively affect the delivered dose conformality in comparison to the plan. We previously demonstrated on volunteers that 3 different modes of mechanically-assisted and non-invasive ventilation (MANIV) may reduce variability in breathing motion. The volume-controlled mode (VC) constraints the amplitude and respiratory rate (RR) in physiologic condition. The shallow-controlled mode (SH), derived from VC, increases the RR and decreases amplitude. The slow-controlled mode (SL) induces repeated breath holds with constrained ventilation pressure. In this study, we compared these mechanical ventilation modes to spontaneous breathing or breath hold and assessed their tolerance and effects on internal tumour motion in patients receiving RT.
The VC and SH modes were evaluated in ten patients with lung or liver cancers (cohort A). The SL mode was evaluated in 12 left breast cancer patients (cohort B). After a training and simulation session, the patients underwent 2 MRI sessions to analyze the internal motion of breast and tumour.
MANIV was well tolerated, without any adverse events or oxymetric changes, even in patients with respiratory comorbidities. In cohort A, when compared to spontaneous breathing (SP), VC reduced significantly inter-session variations of the tumour motion amplitude (p = 0.01), as well as intra- and inter-session variations of the RR (p < 0.05). As to SH, the RR increased, while its variations within and across sessions decreased when compared to SP (p < 0.001). SH reduced the median amplitude of the tumour motion by 6.1 mm or 38.2% (p ≤ 0.01) compared to VC. In cohort B, breast position stability over the end-inspiratory plateaus obtained spontaneously or with SL remained similar. Median duration of the plateaus in SL was 16.6 s.
MANIV is a safe and well tolerated ventilation technique for patients receiving radiotherapy. MANIV could thus make current motion mitigation strategies less critical and more robust. Clinical implementation might be considered, provided the ventilation mode is carefully selected with respect to the treatment indication and patient individualities.

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^☆: Supported in part by grant PO1-CA-59017 from the National Cancer Institute, National Institutes of Health.

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Clinical investigation: LungThe deep inspiration breath-hold technique in the treatment of inoperable non–small-cell lung cancer☆

Abstract

Introduction

Section snippets

DIBH technique

Dosimetry

Discussion

Semin Radiat Oncol

Radiother Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

6 Gy dose levels of a phase I dose escalation study using three dimensional conformal radiotherapy in the treatment of inoperable lung cancer. Int J Radiat Oncol Biol Phys

Radiother Oncol

Int J Radiat Oncol Biol Phys

Radiother Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Ann Oncol

Clinical investigation: Lung
The deep inspiration breath-hold technique in the treatment of inoperable non–small-cell lung cancer☆