Tomotherapy PET-guided dose escalation: A dosimetric feasibility study for patients with malignant pleural mesothelioma

Our plain-English summary of Tomotherapy PET-guided dose escalation: A dosimetric feasibility study for patients with malignant pleural mesothelioma, by A. Maggio, C. Cutaia, A. Di Dia, et al (Strahlentherapie und Onkologie, 2016).

The study

• Authors: A. Maggio, C. Cutaia, A. Di Dia, S. Bresciani, A. Miranti, M. Poli, E. Del Mastro, E. Garibaldi, P. Gabriele, M. Stasi
• Journal: Strahlentherapie und Onkologie
• Published: 2016;192(2):102-8
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Aim: The aim of this study was to investigate whether a safe escalation of the dose to the pleural cavity and PET/CT-positive areas in patients with unresectable malignant pleural mesothelioma (MPM) is possible using helical tomotherapy (HT).

Material And Methods: We selected 12 patients with MPM. Three planning strategies were investigated. In the first strategy (standard treatment), treated comprised a prescribed median dose to the planning target volume (PTV) boost (PTV1) of 64.5 Gy (range: 56 Gy/28 fractions to 66 Gy/30 fractions) and 51 Gy (range: 50.4 Gy/28 fractions to 54 Gy/30 fractions) to the pleura PTV (PTV2). Thereafter, for each patient, two dose escalation plans were generated prescribing 62.5 and 70 Gy (2.5 and 2.8 Gy/fraction, respectively) to the PTV1 and 56 Gy (2.24 Gy/fraction) to the PTV2, in 25 fractions. Dose-volume histogram (DVH) constraints and normal tissue complication probability (NTCP) calculations were used to evaluate the differences between the plans.

Results: For all plans, the 95 % PTVs received at least 95 % of the prescribed dose. For all patients, it was possible to perform the dose escalation in accordance with the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) constraints for organs at risk (OARs). The average contralateral lung dose was < 8 Gy. NTCP values for OARs did not increase significantly compared with the standard treatment (p > 0.05), except for the ipsilateral lung. For all plans, the lung volume ratio was strongly correlated with the V20, V30, and V40 DVHs of the lung (p < 0.0003) and with the lung mean dose (p < 0.0001).

Conclusion: The results of this study suggest that by using HT it is possible to safely escalate the dose delivery to at least 62.5 Gy in PET-positive areas while treating the pleural cavity to 56 Gy in 25 fractions without significantly increasing the dose to the surrounding normal organs.

In plain English

This radiotherapy planning study, from the Candiolo Cancer Institute in Turin, Italy, used the records of 12 patients with malignant pleural mesothelioma (three women and nine men, median age 61) treated with helical tomotherapy, a form of radiation therapy, between February 2012 and March 2014. Their standard plans gave a median 64.5 Gy to areas active on PET scans and 51 Gy to the pleura, in 28 to 30 sessions. For each patient, the authors designed two dose-escalation plans in 25 sessions: 62.5 Gy (2.5 Gy per session) or 70 Gy (2.8 Gy per session) to PET-active areas, plus 56 Gy to the pleura. The authors reported that the escalation plans significantly increased radiation to nearby healthy organs. Even so, every plan stayed within the QUANTEC safety limits, and the average dose to the opposite lung stayed below 8 Gy. The modeled risk of complications rose significantly only for the lung on the tumour side. The authors concluded that giving at least 62.5 Gy to PET-positive areas appeared possible without significantly increasing risk to surrounding organs. With few patients, they did not test whether doses related to actual lung side effects. Asbestos exposure was not studied.

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: Dosimetric (radiotherapy treatment-planning) feasibility study comparing a standard plan with two dose-escalation plans for each patient
• Who was studied: 12 consecutive patients with histologically confirmed malignant pleural mesothelioma treated with helical tomotherapy at the Candiolo Cancer Institute, Turin, Italy, between February 2012 and March 2014. Three were female and nine male. Eight had right-sided disease and four had left-sided disease. The median age was 61 years (range 50 to 73).
• Exposure: Radiation dose plans, not asbestos exposure. The standard treatment had a median 64.5 Gy (range 56 Gy in 28 fractions to 66 Gy in 30 fractions) to PET-positive target areas (PTV1). It gave 51 Gy (range 50.4 Gy in 28 fractions to 54 Gy in 30 fractions) to the pleura (PTV2). Two escalation plans prescribed 62.5 Gy (2.5 Gy per fraction) or 70 Gy (2.8 Gy per fraction) to PTV1, together with 56 Gy (2.24 Gy per fraction) to PTV2, in 25 fractions. The 62.5 Gy prescription is lower in total than the standard median of 64.5 Gy, but it is given in fewer, larger fractions.
• Main results:
  • In all plans, 95% of the planning target volumes received at least 95% of the prescribed dose.
  • Compared with the standard treatment, the dose escalation significantly increased the dose to organs at risk.
  • For all 12 patients and all plans, the escalation met the QUANTEC organ-at-risk limits. The average dose to the contralateral (opposite) lung was kept below 8 Gy.
  • For strategies II and III, the mean contralateral lung V5 Gy was slightly higher than the limit proposed by Patel et al.
  • Calculated normal tissue complication probabilities did not rise significantly compared with standard treatment (p greater than 0.05), except for the ipsilateral lung, the lung on the tumour side (p less than 0.0001). In Table 1, the average ipsilateral lung complication probability was 88.7 (plus or minus 4.4) for standard treatment, 96.7 (plus or minus 1.7) for strategy II and 96.9 (plus or minus 5.2) for strategy III.
  • Across the three strategies, the ratio of ipsilateral to contralateral lung volume was strongly correlated with lung V20, V30 and V40 values (R greater than 0.881, p less than 0.0003). The same ratio was strongly correlated with mean lung dose (R greater than 0.94, p less than 0.0001). Total lung volume was not correlated with V20, V30 or V40.
• The authors' conclusion: The authors concluded that helical tomotherapy may allow a safe escalation to at least 62.5 Gy in PET-positive areas, with 56 Gy in 25 fractions to the pleural cavity, without significantly increasing toxicity risk to surrounding normal organs. They wrote that these results support starting a phase I to II clinical trial with up to 70 Gy to PTV1.
• Limitations the authors state:
  • Because few patients were treated, the authors did not analyse whether the dose measures correlated with actual lung toxicity in patients.
  • Little is known about side effects in the ipsilateral lung, part of which lies inside the target volume, especially at high doses to PET-positive areas.

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, Pleural Cavity, Unresectable, Pleura.

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