Three-dimensional conformal radiation therapy for non–small-cell lung cancer: A Phase I/II dose escalation clinical trial☆

Three-dimensional conformal radiation therapy for non–small-cell lung cancer: A Phase I/II dose escalation clinical trial☆
Kai-Liang Wu, M.D., Guo-Liang Jiang, M.D., Yuan Liao, Ph.D., Hao Qian, M.D., Li-Juan Wang, M.D., Xiao-Long Fu, M.D., Shen Zhao, M.D.

Purpose
A prospective Phase I/II dose escalation study was conducted to determine the maximum tolerated dose (MTD) in three-dimensional conformal radiation therapy (3D-CRT) for non–small-cell lung cancer (NSCLC).

Methods and materials
MTD would be reached via a dose escalation study. After 42 Gy/21 fractions, 4.2 weeks by conventional fractionated irradiation through anteroposterior/posteroanterior fields, the 3D-CRT technique was used as boost. The planned total dose escalation depended on lung volume irradiated. According to the percentage of lung volume receiving >20 Gy, the patients were divided into three subgroups (i.e., <25%, 25%–37%, and >37%). The scheduled dose escalation began with 69 Gy and continued to 78 Gy. The boost doses were delivered at 3 Gy per fraction, once per day, five fractions per week. Each dose level includes 5 patients. Besides radiotherapy, all patients received neoadjuvant and adjuvant chemotherapy with MVP regimen (Mitomycin, Vindesine, cis-platium). The criterion for stopping further dose escalation was ≥20% of patients with ≥RTOG Grade 3 radiation pneumonitis.

Results
Between June 1999 and February 2001, 50 patients had been enrolled in this study, including 4 with Stage II disease, 31 with Stage IIIa disease, and 15 with Stage IIIb disease. The dose escalation plan has been completed. All subgroups reached the highest predetermined dose levels (i.e., 78 Gy for the <25% subgroup, 78 Gy for the 25–37% subgroup, and 75 Gy for the >37% subgroup). Although none of the subgroups developed more than 20% of ≥Grade 3 acute pneumonitis, dose escalation was terminated because long-term follow-up was needed to observe late complications. Median follow-up time (MFT) for the entire group was 18 months (6–37 months). The most common acute complication was esophagitis in 56% of patients with RTOG Grade 1–2, and in 4% with Grade 3. Acute radiation pneumonitis developed in 36% of patients with RTOG Grade 1–2. Only 1 patient had Grade 3 pneumonitis, which was in the 25–37% subgroup at 75 Gy. The hematopoietic toxicity appeared in 58% of patients with Grade 1–2, and 8% with Grade 3. As to late complications, only 30% of patients developed pulmonary fibrosis of RTOG Grade 1–2. The median survival time for the entire group was 18 months. Two-year overall survival, locoregional progression-free rate, and distant metastasis rate were 44%, 40%, and 41%, respectively.

Conclusion
Although MFT was 18 months, it had not yet been declared because a longer follow-up was needed to observe the late complications. The 2-year overall survival of 44% was very encouraging and implied that 3D-CRT combined with chemotherapy would improve the outcome for locally advanced NSCLC.

CRUK/07/001: QUARTZ - A phase III multicentre randomised trial to assess dexamethasone +/- whole brain radiotherapy in patients with inoperable brain

Paula Mulvenna
Medical Research Council
01 January 2007 to 31 December 2013
Clinical Trials Awards & Advisory Committee - Late Phase Study
Funding committee - Clinical Trials Awards and Advisory Committe

Cerebral metastases, from any primary, are a devastating occurrence and most patients deteriorate quickly over a matter of weeks. A number of treatment options have been investigated, but for many years, the standard therapy for patients with inoperable brain metastases has remained a combination of steroids and Whole Brain Radiotherapy (WBRT). However, WBRT can be toxic and has not been shown to consistently improve length or quality of survival, particularly for patients with a non-small cell lung cancer primary.
The aim of this trial is to determine whether dexamethasone alone is as effective as dexamethasone plus WBRT in terms of overall quality of survival time for patients with inoperable brain metastases originating from non-small cell lung cancer, when both groups of patients are also receiving optimal supportive care At the time of referral to the oncology centre, the vast majority of patients will be receiving optimal supportive care (OSC) including dexamethasone for symptom relief. Patients will continue to receive this treatment and in addition will be allocated WBRT (20 Gy in 5 consecutive daily fractions) or not. Because these patients have a short survival time, and may not be well enough to be seen in clinic; a nurse will assess all patients via a weekly telephone call.

IMRT IN LYMPHOMA CANCER

http://video.about.com/lymphoma/IMRT.htm

Induction Chemotherapy versus Chemoradiotherapy for Stage III Non-small Cell Lung Cancer

David Muñoz Carmona

ASTRO 2008

Reviewer: Nathan Jones DO

Abramson Cancer Center of the University of Pennsylvania

Posting Date: September 23, 2008

Presenter: Kristin Higgins

Presenter's Affiliation: Duke University, North Carolina

Type of Session: Scientific

Background

• Stage IIIa non-small cell lung cancer with N2 disease represents a heterogenous group of patients ranging from microscopic lymph node involvement on staging mediastinoscopy to bulky mediastinal disease on initial staging
• The optimal treatment for these patients remains controversial
• As surgery alone has shown poor outcomes, pre-operative treatment appears to be more efficacious
• There is no consensus of the superiority of chemotherapy alone versus chemoradiation in the neoadjuvant setting
• This study sets out to compare these two approaches and to identify subgroups that may benefit from the more aggressive chemoradiation approach

Materials and Methods

• Retrospective analysis of 101 patients treated at Duke from 1995-2006
• All patients with pathologically demonstrated N2 disease
• All patients underwent induction therapy consisting of chemotherapy alone or chemoradiation, in anticipation of definitive surgery
• Multivariate analysis was performed to assess the effect of various factors on overall survival, disease-free survival and local control
• Kaplan-Meier curves were utilized to compare local control, disease-free survival, and overall survival

Results

• 101 patients were included in the analysis, with approximately 2/3 receiving chemoradiation
• 3-year overall survival was 40% for all patients, with no significant difference between those receiving chemotherapy alone or chemoradiation
• Pathologic complete response (CR) rate was 65% vs 35%, favoring those receiving chemoradiation
• Post-operative mortality was 5% in both groups
• There was a trend towards those patients receiving chemoradiation being more likely to ultimately undergo resection (84% vs 69% of those receiving chemotherapy alone, p=0.1)
• All patients receiving neoadjuvant therapy were included in the analysis, regardless of whether or not surgery was ultimately performed
• Bronchopleural fistula occurred in 7% of chemoradiation patients vs 0% of chemotherapy patients, but this did not reach statistical significance (p=0.27)
• Multivariate analysis demonstrated that pathologic CR was significantly associated with local control and disease-free survival, but not overall survival
• 3-year overall survival for macroscopic vs microscopic N2 disease was 48% vs 32% (p=0.2)
• Overall survival curves among patients with lymph nodes ≥ 1cm appeared to separate favoring chemoradiation, but did not reach statistical significance (p=0.22), while among patients with lymph nodes < p="0.12)">

Author's Conclusions

• These data demonstrate no clinically significant difference in outcomes for patients with stage IIIa N2 non-small cell lung cancer based on pre-operative treatment
• No subgroup was identified which would benefit from the combined modality approach
• Pre-operative chemoradiation did appear to offer improved pathologic CR rate, which correlated with disease-free survival and local control, but not overall survival

Clinical/Scientific Implications

• Optimal treatment of stage III non-small cell lung cancer remains controversial
• EORTC 08941 demonstrated similar 5-year overall survival for patients treated with neoadjuvant chemotherapy and randomized to surgery versus definitive radiation therapy, with the suggestion that forgoing surgery results in decreased morbidity
• These data are limited by the retrospective nature of the study, uneven sized arms, and the great potential for treatment bias between the two groups
• Additional data are necessary before one can support the practice of categorical omission of radiation in the neoadjuvant setting for stage IIIa NSCLC patients