Hyperfractionated or Accelerated Radiotherapy in Lung Cancer: An Individual Patient Data Meta-Analysis

Mauguen, Audrey; Péchoux, C. Le; Saunders, Michele I.; Schild, Steven E.; Turrisi, Andrew T.; Baumann, Michaël; Sause, William T.; Ball, David; Belani, Chandra P.; Bonner, James A.; Zajusz, Aleksander; Dahlberg, Suzanne E.; Nankivell, Matthew; Mandrekar, Sumithra J.; Paulus, Rebecca; Behrendt, K.; Koch, Rainer; Bishop, James F.; Dische, Stanley; Arriagada, R.; Ruysscher, Dirk De; Pignon, Jean-Pierre

doi:10.1200/jco.2012.41.6677

Cited by 216 publications

(132 citation statements)

References 39 publications

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“…In our study, we delivered the intended doses to the targets while respecting OAR constraints in most cases. Moreover, in a considerable number of cases, the limited doses delivered to the different OARs could open a window for dose intensification.With only 5% of grade 3 oesophagitis, our results compare favorably with those reported in the literature, 3,4 indicating that the dosimetric gain has a clinical impact on the incidence of AET. Even if acute oesophagitis has been considered reversible, it is responsible for treatment interruptions and dose reductions.…”

supporting

confidence: 80%

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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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supporting

confidence: 80%

“…With only 5% of grade 3 oesophagitis, our results compare favorably with those reported in the literature, 3,4 indicating that the dosimetric gain has a clinical impact on the incidence of AET. Even if acute oesophagitis has been considered reversible, it is responsible for treatment interruptions and dose reductions.…”

supporting

confidence: 80%

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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“…This might improve prognosis through lower locoregional recurrences and higher resection rates. A recent meta-analysis comparing modified RT schedules with conventional RT reported that patients with nonmetastatic NSCLC derived a significant OS benefit from accelerated or hyperfractionated radiotherapy (24).…”

Section: Neoadjuvant Hyperfractionated Radiotherapy With Chemotherapymentioning

confidence: 99%

Neoadjuvant Radiotherapy/Chemoradiotherapy in Locally Advanced Non-Small Cell Lung Cancer

Yalman¹

2015

Balkan Med J

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Approximately one third of non-small cell lung cancer (NSCLC) patients present with locally advanced disease (stages IIIA/IIIB), and since this is an extremely heterogeneous group, the optimal treatment is still controversial. The current standard of care in these patients is concurrent chemoradiotherapy. However, the prognosis is poor, with high rates of local and distant failure, and five-year overall survival (OS) rates ranging between 15% and 25% (1). In a minority of selected patients, one approach that has improved outcomes is the use of a combination of neoadjuvant chemotherapy (CT), radiotherapy (RT), and surgery. The aims of neoadjuvant treatment are to improve resectability by shrinking the tumor,

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“…A recent meta-analysis by Mauguen et al (15) evaluated ten trials including 2,000 patients and concluded that modifying the radiotherapy schedule by HyperFRT, ART or both resulted in an increase of overall survival. Employing altered fractionation reduced the risk of death by 12% and enhanced the 3-and 5-year survival rates, as an absolute overall survival increment was succeeded by 3.8% at 3 years and 2.5% at 5 years.…”

Section: Treatment Duration and Altered Fractionationmentioning

confidence: 99%

Definitive Radiotherapy in Locally Advanced Non-Small Cell Lung Cancer: Dose and Fractionation

Dağoğlu¹,

Sule²,

Arifoglu³

et al. 2015

Balkan Med J

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Lung cancer is the leading cause of cancer-related mortality for both men and women. Among all cases, non-small cell lung cancer (NSCLC) accounts for 70-80% and almost half of the cases are considered to be locally advanced (LA) or unresectable disease at first presentation (1). Until only a decade ago, conventional fractionated radiotherapy (RT) alone applied at a dose of 60 Gy in 2 Gy fractions over 6 weeks was accepted as the standard nonsurgical treatment for these patients. However, the results were discouraging as the median survival obtained was less than a year and the 2-year survival rate did not go above 15-20% (2).After the impact of RT dose for lung cancer was established (3), a number of trials were structured in the quest for better local control and overall survival by either dose escalation or shortening the total treatment time through conventional/altered fractionation, even in combination with chemotherapy (CT) and other targeted agents.This review summarises the results of significant trials on dose and altered fractionation in the treatment of LA-NSCLC with an emphasis on possible future perspectives. The included trials were evaluated under two main titles as "Dose and Dose Escalation" and "Treatment Duration and Altered Fractionation". It should be noted that there is not always a distinct differentiation among the trials as some of the studies address both aspects. In the case of overlap, trials were grouped according to the main hypothesis which they were designed to answer. DOSE AND DOSE ESCALATIONSeveral studies have confirmed the relationship for dose and tumour response that led to an ameliorated local control and survival (Table 1).The first trial that validated the advantage of dose escalation for LA-NSCLC was the Radiation Therapy Oncology Group (RTOG) 73-01 trial, where 376 patients were randomised into four arms (2). Three arms included standard fractionation with doses of 40, 50 and 60 Gy in 2 Gy fractions and the fourth arm included a split course RT that was applied in 4 Gy fraction size to a total dose of 40 Gy over 5 weeks with a 3 week interruption in the middle. The overall 3 year intrathoracic failure rate was 33% for patients treated in the 60 Gy arm; this was significantly lower when compared to the other arms, with reDefinitive radiotherapy plays a major role in the treatment of locally advanced non-small cell lung cancer (LA NSCLC). After the impact of RT dose for lung cancer was established, a number of trials were structured with the aim of better local control and overall survival by either dose escalation or shortening the total treatment time through conventional/altered fractionation, even in combination with chemotherapy (CT) and other targeted agents. In spite of the increased number of these studies, the optimal dose or fractionation still remains to be determined. Another aspect questioned is the incorporation of these higher doses and shorter treatment times with chemotherapy or targeted agents. This review summarises the results of significant trials on d...

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Hyperfractionated or Accelerated Radiotherapy in Lung Cancer: An Individual Patient Data Meta-Analysis

Abstract: Patients with nonmetastatic NSCLC derived a significant OS benefit from accelerated or hyperfractionated radiotherapy; a similar but nonsignificant trend was observed for SCLC. As expected, there was increased acute esophageal toxicity.

Cited by 216 publications

References 39 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

Neoadjuvant Radiotherapy/Chemoradiotherapy in Locally Advanced Non-Small Cell Lung Cancer

Definitive Radiotherapy in Locally Advanced Non-Small Cell Lung Cancer: Dose and Fractionation

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