PET-guided dose escalation tomotherapy in malignant pleural mesothelioma

Our plain-English summary of PET-guided dose escalation tomotherapy in malignant pleural mesothelioma, by A. Fodor, C. Fiorino, I. Dell'Oca, et al (Strahlentherapie und Onkologie, 2011).

The study

• Authors: A. Fodor, C. Fiorino, I. Dell'Oca, S. Broggi, M. Pasetti, G.M. Cattaneo, L. Gianolli, R. Calandrino, N.G. Di Muzio
• Journal: Strahlentherapie und Onkologie
• Published: 2011;187(11):736-43
• Cited by: 27 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: To test the feasibility of salvage radiotherapy using PET-guided helical tomotherapy in patients with progressive malignant pleural mesothelioma (MPM).

Patients And Methods: A group of 12 consecutive MPM patients was treated with 56 Gy/25 fractions to the planning target volume (PTV); FDG-PET/CT simulation was always performed to include all positive lymph nodes and MPM infiltrations. Subsequently, a second group of 12 consecutive patients was treated with the same dose to the whole pleura adding a simultaneous integrated boost of 62.5 Gy to the FDG-PET/CT positive areas (BTV).

Results: Good dosimetric results were obtained in both groups. No grade 3 (RTOG/EORTC) acute or late toxicities were reported in the first group, while 3 cases of grade 3 late pneumonitis were registered in the second group: the duration of symptoms was 2-10 weeks. Median overall survival was 8 months (1.2-50.5 months) and 20 months (4.3-33.8 months) from the beginning of radiotherapy, for groups I and II, respectively (p=0.19). A significant impact on local relapse from radiotherapy was seen (median time to local relapse: 8 vs 17 months; 1-year local relapse-free rate: 16% vs 81%, p=0.003).

Conclusions: The results of this pilot study support the planning of a phase III study of combined sequential chemoradiotherapy with dose escalation to BTV in patients not able to undergo resection.

In plain English

This non-randomized pilot study tested whether PET-guided helical tomotherapy, a radiotherapy technique, was feasible for 24 patients with malignant pleural mesothelioma that was progressing after earlier surgery and/or chemotherapy. The first 12 patients (2006 to 2007) were prescribed 56 Gy in 25 fractions. One patient's treatment stopped at 31.2 Gy, and another received an extra fraction. The next 12 (2008 to 2009) were prescribed 56 Gy to the whole pleura while, during the same treatment, PET-active areas received 62.5 Gy in total. One of them instead received 54 Gy and 60 Gy respectively. No grade 3 side effects were reported in the first group. In the boosted group, 3 of 12 were hospitalized with grade 3 late radiation pneumonitis, and all recovered. One-year overall survival was 41% without the boost versus 59% with it (p = 0.19, not statistically significant). The boosted group had a longer median time to local relapse (17 versus 8 months) and a higher 1-year local relapse-free rate (81% versus 16%, p = 0.003). The authors concluded that dose escalation improved local control and suggested a phase III trial. They wrote that a survival benefit could not be shown, probably because of the small number of patients.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Two-step nonrandomized dose escalation pilot (feasibility) study comparing two consecutive treatment groups
• Who was studied: 24 consecutive patients with malignant pleural mesothelioma at San Raffaele Scientific Institute, Milan, Italy. All had progression or relapse after surgery and/or chemotherapy and had not previously been irradiated on the same-side pleura or lung. Group I had 12 patients treated May 2006 to November 2007. Group II had 12 patients treated March 2008 to April 2009.
• Exposure: Radiotherapy, not asbestos (asbestos exposure is not discussed). Group I was prescribed 56 Gy in 25 fractions to the planning target volume. Group II was prescribed the same 56 Gy in 25 fractions to the planning target volume while the PET-positive subvolumes (biological target volume) were given 62.5 Gy concomitantly, as a simultaneous integrated boost. There were individual exceptions in each group (see results).
• Main results:
  • In group I, delivered doses ranged from 31.2 to 58.24 Gy. The extrapleural pneumonectomy patient's radiotherapy was interrupted at 31.2 Gy, and one patient received an extra fraction to make up for an interruption caused by machine failure.
  • In group II, one patient received 54 Gy to the planning target volume and 60 Gy to the PET-positive volume, to reduce the kidney dose because of earlier irradiation for seminoma.
  • No grade 3 acute or late toxicities were reported in group I (no boost). In group II (boost) there were 3 cases of grade 3 late pneumonitis.
  • Three boost-group patients needed hospitalization for actinic pneumonitis 2 to 6 weeks after the end of radiotherapy. All three recovered.
  • Two group I patients died within 1 month of the end of radiotherapy. Based on clinical statements, treatment was not considered the cause.
  • Acute grade 2 dermatitis and late grade 3 pneumonitis were increased in the boost group compared with group I (p = 0.07).
  • The mean dose to the same-side lung outside the clinical target volume was 4 Gy higher in the boost group (p = 0.01). The authors suggested this could explain the increased lung toxicity.
  • In the boost group, lung toxicity occurred in 5 of 6 patients with a PET-positive volume under 180 ml and in 1 of 6 with a volume over 180 ml (p = 0.04).
  • In both groups, the mean dose to the opposite-side lung was under 8 Gy.
  • One-year overall survival was 41% in group I versus 59% in the boost group. The difference was not statistically significant (log-rank p = 0.19).
  • Median time to any relapse (local and distant) was 11 months in the boost group versus 8 months in group I. The difference was not significant (p = 0.19).
  • Median time to local relapse was 8 months in group I and 17 months in the boost group. The 1-year local relapse-free rate was 16% versus 81% (log-rank p = 0.003).
  • One-year cancer-specific survival was 46% in group I versus 71% in the boost group (p = 0.12).
• The authors' conclusion: The authors concluded that local control improved significantly when the dose was escalated on PET-positive volumes with tomotherapy. They suggested a multi-institutional phase III study comparing no-boost and boost radiotherapy after pemetrexed and cisplatin chemotherapy in unresectable patients.
• Limitations the authors state:
  • The authors stated that an improvement in overall survival with dose escalation could not be demonstrated, probably because of the limited number of patients.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Pleura, Pneumonitis, Median Overall Survival.

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• Prognostic value of 18F-FDG standard uptake value by integrated PET/CT in the staging of malignant pleural mesothelioma — G. Genestreti, A. Moretti, et al. (2012)
• FDG PET/CT in the management of primary pleural tumors and pleural metastases — M. Kruse, S.J. Sherry, et al. (2013)
• Clinical implications of 18F-fluorodeoxyglucose positron emission tomography/computed tomography at delayed phase for diagnosis and prognosis of malignant pleural mesothelioma — Y. Abe, K. Tamura, et al. (2012)
• Moderately Hypofractionated Helical IMRT, FDG-PET/CT-guided, for Progressive Malignant Pleural Mesothelioma in Patients With Intact Lungs — A. Fodor, S. Broggi, et al. (2019)

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