Severe late esophagus toxicity in NSCLC patients treated with IMRT and concurrent chemotherapy

Chen, Chun; Uyterlinde, Wilma; Sonke, Jan‐Jakob; Bois, Josien de; Heuvel, Michel van den; Belderbos, J.

doi:10.1016/j.radonc.2013.08.017

Cited by 48 publications

(42 citation statements)

References 18 publications

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“…Even if acute oesophagitis has been considered reversible, it is responsible for treatment interruptions and dose reductions. In fact a recent publication 9 showed a consequential effect between acute oesophagitis intensity and late oesophageal strictures. Therefore, a reduction in the incidence of severe oesophageal toxicity remains a major clinical concern in thoracic irradiation.…”

Section: Discussionmentioning

confidence: 98%

Simultaneously modulated accelerated radiation therapy reduces severe oesophageal toxicity in concomitant chemoradiotherapy of locally advanced non-small-cell lung cancer

Chajon¹,

Bellec²,

Castelli³

et al. 2015

BJR

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Objective: The aim of this study was to evaluate the potential of simultaneously modulated accelerated radiation therapy (SMART) to reduce the incidence of severe acute oesophagitis in the treatment of unresectable locally advanced non-small-cell lung cancer (LANSCLC). Methods: 21 patients were treated with SMART and concomitant platinum-based chemotherapy. The prescribed doses were limited to 54 Gy at 1.8 Gy per day to the zones of presumed microscopic extent while simultaneously maintaining doses of 66 Gy at 2.2 Gy per day to the macroscopic disease. The whole treatment was delivered over 30 fractions and 6 weeks. . With a median follow-up of 18 months (6-33 months), the 1-year local control rate was 70% and the disease-free survival rate was 47%. Conclusion: SMART reduces the incidence of severe oesophagitis and improves the whole dosimetric predictors of toxicity for the lung, heart and spine. Advances in knowledge: Our study shows that SMART optimizes the therapeutic ratio in the treatment of LANSCLC, opening a window for dose intensification. INTRODUCTIONConcurrent chemoradiotherapy is the standard of care for the treatment of unresectable locally advanced non-smallcell lung cancer (LANSCLC). 1 Acute oesophageal toxicity (AET) is the main acute limiting toxicity related to this approach, and is responsible for weight loss, insertion of tube feeding, hospital admissions and treatment discontinuation. A recent meta-analysis showed that hyperfractionated or accelerated radiotherapy (RT) schedules improve survival rates;3 however, when chemotherapy is associated concomitantly with these schedules, the incidence of severe oesophagitis of around 22% remains a subject of concern. 4 In the RT planning process, the delineation of target volumes to be treated is an obligatory step. The gross demonstrable disease is named gross tumour volume (GTV) and encompasses the primary tumour and the metastatic lymph nodes identified by the endoscopic and radiologic examinations. The microscopic tumour spread, outside of what can be visualized in a particular imaging modality, is named clinical target volume (CTV) and corresponds to a volume of tissue surrounding the primary tumour and the lymph node stations considered at risk of failure. 5 In the standard technique of RT, a homogeneous dose of 66 Gy at 2 or 1.8 Gy per fraction and per day is delivered to the GTV and CTV. In contrast to this standard technique, simultaneously modulated accelerated radiation therapy (SMART) is a technique delivering 66 Gy by using high fraction doses (2.2 Gy per fraction) to the GTV simultaneously with standard fraction doses (1.8 Gy per fraction) to regions of presumed microscopic extent (CTV), devised in such a manner that the biologically effective GTV dose is equivalent to 70 Gy delivered by conventional (2 Gy per fraction) fractionated RT. This regimen is delivered over 6 weeks, representing a moderate acceleration over a standard course. As proved in head and neck cancer, this technique lead to a moderate GTV dose acceleration without inc...

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Section: Discussionmentioning

confidence: 98%

Simultaneously modulated accelerated radiation therapy reduces severe oesophageal toxicity in concomitant chemoradiotherapy of locally advanced non-small-cell lung cancer

Chajon¹,

Bellec²,

Castelli³

et al. 2015

BJR

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“…The parameters used were n=1.04, m=0.65, and D 50 =32.84 Gy in the Wijsman model. The Chen model is also an LKB-based model derived from 171 NSCLC patients treated with CCRT, and we used this model to predict the incidence of late esophageal toxicity (LET) 31. The parameters used were n=0.03, m=0.03, and TD 50 =76.1 Gy in this model.…”

Section: Methodsmentioning

confidence: 99%

Radiobiological evaluation of simultaneously dose-escalated versus non-escalated intensity-modulated radiation therapy for patients with upper thoracic esophageal cancer

Huang

Guo

et al. 2017

OTT

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ObjectiveTo compare the radiobiological response between simultaneously dose-escalated and non-escalated intensity-modulated radiation therapy (DE-IMRT and NE-IMRT) for patients with upper thoracic esophageal cancer (UTEC) using radiobiological evaluation.MethodsComputed tomography simulation data sets for 25 patients pathologically diagnosed with primary UTEC were used in this study. DE-IMRT plan with an escalated dose of 64.8 Gy/28 fractions to the gross tumor volume (GTV) and involved lymph nodes from 25 patients pathologically diagnosed with primary UTEC, was compared to an NE-IMRT plan of 50.4 Gy/28 fractions. Dose-volume metrics, tumor control probability (TCP), and normal tissue complication probability for the lung and spinal cord were compared. In addition, the risk of acute esophageal toxicity (AET) and late esophageal toxicity (LET) were also analyzed.ResultsCompared with NE-IMRT plan, we found the DE-IMRT plan resulted in a 14.6 Gy dose escalation to the GTV. The tumor control was predicted to increase by 31.8%, 39.1%, and 40.9% for three independent TCP models. The predicted incidence of radiation pneumonitis was similar (3.9% versus 3.6%), and the estimated risk of radiation-induced spinal cord injury was extremely low (<0.13%) in both groups. Regarding the esophageal toxicities, the estimated grade ≥2 and grade ≥3 AET predicted by the Kwint model were increased by 2.5% and 3.8%. Grade ≥2 AET predicted using the Wijsman model was increased by 14.9%. The predicted incidence of LET was low (<0.51%) in both groups.ConclusionRadiobiological evaluation reveals that the DE-IMRT dosing strategy is feasible for patients with UTEC, with significant gains in tumor control and minor or clinically acceptable increases in radiation-induced toxicities.

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“…However, in our study, grade 3 patients had a low recovery rate (48%) within 3 months and a long median duration (>80 days). We concluded that 52% of grade 3 patients are subjective to a risk of developing late esophagus toxicity, which in the severe cases (e.g., stenosis and fistula) could deteriorate the long-term quality of life, or even compromise survival (15).…”

Section: Acute Esophagus Toxicitymentioning

confidence: 96%

“…This knowledge was used for initiating proactive supportive care management, patient education and the recalculation of RT restraints (13)(14)(15) …”

Section: Introductionmentioning

confidence: 99%

Overcoming toxicity-challenges in chemoradiation for non-small cell lung cancer

Uyterlinde

2016

Transl. Lung Cancer Res.

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Concurrent chemoradiation (CCRT) is the treatment of choice for locally advanced non-small cell lung cancer (NSCLC) with a modest survival benefit over sequential chemoradiation or radiotherapy (SCRT) alone. However, this benefit is at the cost of increasing acute toxicity such as esophagitis. Previous analysis revealed several predictive parameters in dose-volume and patient characteristics which helped us to identify those patients at risk for severe esophagus toxicity. As a result, supportive care interventions including individualized patient information, dietary guidance, adequate medication, hydration and tubefeeding could be initiated. This paper discusses the challenges in overcoming chemoradiation induced acute esophageal toxicity (AET).

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Severe late esophagus toxicity in NSCLC patients treated with IMRT and concurrent chemotherapy

Cited by 48 publications

References 18 publications

Simultaneously modulated accelerated radiation therapy reduces severe oesophageal toxicity in concomitant chemoradiotherapy of locally advanced non-small-cell lung cancer

Simultaneously modulated accelerated radiation therapy reduces severe oesophageal toxicity in concomitant chemoradiotherapy of locally advanced non-small-cell lung cancer

Radiobiological evaluation of simultaneously dose-escalated versus non-escalated intensity-modulated radiation therapy for patients with upper thoracic esophageal cancer

Overcoming toxicity-challenges in chemoradiation for non-small cell lung cancer

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