Radioterapia ipofrazionata nel NSCLC localmente avanzato. Evidenze - - PowerPoint PPT Presentation

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Radioterapia ipofrazionata nel NSCLC localmente avanzato. Evidenze - - PowerPoint PPT Presentation

Nov 07, 2022 330 likes •871 views

Neoplasie del Polmone Radioterapia ipofrazionata nel NSCLC localmente avanzato. Evidenze cliniche e prospettive. Marco Trov CRO Aviano Gruppo di Studio AIRO Polmone DICHIARAZIONE Relatore: Marco Trov Come da nuova regolamentazione

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Radioterapia ipofrazionata nel NSCLC localmente avanzato. Evidenze cliniche e prospettive.

Marco Trovò – CRO Aviano Gruppo di Studio AIRO Polmone

Neoplasie del Polmone

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DICHIARAZIONE Relatore: Marco Trovò

Come da nuova regolamentazione della Commissione Nazionale per la Formazione Continua del Ministero della Salute, è richiesta la trasparenza delle fonti di finanziamento e dei rapporti con soggetti portatori di interessi commerciali in campo sanitario.

  • Posizione di dipendente in aziende con interessi commerciali in campo sanitario (NIENTE DA DICHIARARE)
  • Consulenza ad aziende con interessi commerciali in campo sanitario (NIENTE DA DICHIARARE)
  • Fondi per la ricerca da aziende con interessi commerciali in campo sanitario (NIENTE DA DICHIARARE)
  • Partecipazione ad Advisory Board (NIENTE DA DICHIARARE)
  • Titolarietà di brevetti in compartecipazione ad aziende con interessi commerciali in campo sanitario (NIENTE DA

DICHIARARE)

  • Partecipazioni azionarie in aziende con interessi commerciali in campo sanitario (NIENTE DA DICHIARARE)
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RTOG 0617

INTRODUCTION

RTOG 0617

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INTRODUCTION

RTOG 0617

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doseline

‘73-‘80 60 Gy

2D-RT 3D-CRT

’93-’00 83 Gy ’03-’05

Concomitant Chemotherapy

IMRT

FDG-PET/CT

74 Gy ’06-’11

RTOG 0617 60 Gy vs.74 Gy

60

Post RTOG 0617 era

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‘80 60 Gy 2D- RT 3D-CRT ’93-’00 83 Gy ’03-’0 5 IMRT 74 Gy ’06-’11 60 Gy Post RTOG 0617 era 2013

SBRT ? Hypofractionation?

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!

Re-irradiazione: standard clinico o ricerca?

Re-irradiazione neoplasie toraciche

Marco Trovò Rimini, 9 Novembre 2015

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Hypofractionation

  • Rationale
  • Clinical data
  • Points of discussion
  • Future directions
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Hypofractionation

  • Rationale
  • Clinical data
  • Points of discussion
  • Future directions
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Rationale for Hypofractionation

  • 1. Radiation fraction size

α/β is not favorable in lung cancer! Tumors might be heterogeneous, with clones which respond more like late- responding tissue.

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Rationale for Hypofractionation

  • 2. Repopulation

It might be benefitial to employ shortened regimen

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Rationale for Hypofractionation

  • 3. Volume effect

n: effect/volume parameter

  • n  0: serial organ (ex. cord): toxicity

related to “dose effect”

  • n  1: parallel organ (ex. lung): toxicity

related to “volume effect”

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  • Tumori. 1992 Oct 31;78(5):305-10.

Unfavorable experience with hypofractionated radiotherapy in unresectable lung cancer. Pirtoli L1, Bindi M, Bellezza A, Pepi F, Tucci E.

The use of a reduced number of large-sized fractions in radiotherapy (hypofractionation) is usually associated with poor therapeutic results and severe adverse effects, in accord with radiobiologic concepts. However by some authors unresectable lung cancer patients have been treated with hypofractionated radiotherapy with the main aim of "convenience". Result and damage rates are reported to be comparable to those of conventional treatment. In our experience, based on palliative irradiation of 86 advanced-stage, nonmicrocytoma patients, objective remission rates, subjective and performance status improvement, and survival overall were as poor as could be expected in this kind of presentation, with no striking impact of this treatment modality. Severe adverse effects were shown by a large proportion of cases involving skin and soft tissues of the chest wall (40%) and lungs (55.5%). The incidence of severe damage was in agreement with BED (biologic effective dose) values, differently from other experiences of radiotherapeutic management of advanced lung cancer with large fractions.

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Hypofractionation

  • Rationale
  • Clinical data
  • Points of discussion
  • Future directions
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Kaster TS. Clin Lung Cancer 2015

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Kaster TS. Clin Lung Cancer 2015

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Main Limitations:

  • No robust and reliable toxicity data
  • Palliative treatments
  • ENI
  • No PET or IMRT
  • Retrospective studies
  • Prospective although observational studies
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Radiotherapy Alone.

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609 patients 55 Gy in 20 fr @2.75 Gy/fr OS:

  • median: 24 mo
  • 2-year: 50%

Grade II pneumonitis: 20%

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Considerations:

  • 200 patients were stage I
  • GTV-PTV margin: 15-20 mm
  • No PET
  • Toxicity recorded in 378 patients
  • No Grade ≥3 Toxicity
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30 patients (stage III 77%; stage IV 23%) 60 Gy @3Gy/fr Induction chemo 80% Median PTV: 335 cc (range 73-682) LRR: 37% 2-Y OS: 38%.

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Radiotherapy + Chemotherapy.

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130 Stage III NSCLC pt. R VNB+CDDPx4  55Gy/ 20 fr (2.75 Gy/fr) VNB+CDDP + 55Gy/20 fr

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RT details:

  • Lung V20 < 35%
  • PET + disease (no ENI)
  • GTVPTV 1.5 cm
  • No IMRT
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SOCCAR Concomitant Sequential Compliance to RT 95% 78% Grade 3-5 toxicity 34% 41% Mortality 2.9% 1.7% Grade 3 pneumonitis 3% 5% Median OS 24 mo 18 mo

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102 Stage II-III NSCLC R 66 Gy/24fr (2.75Gy/fr) + daily CDDP 66 Gy/24fr + daily CDDP + Cetuximab

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RT details:

  • MLD< 20 Gy
  • PET + disease (no ENI)
  • GTVPTV 1.2 cm
  • IMRT 75%
  • IGRT
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Results:

  • Compliance to RT: 84%-88%.
  • Grade 3-5 tox: 45% - 65%
  • Grade 3 Pneumonitis: 0% - 6%
  • Median OS: 31 mo (no difference)
  • 2y OS = 60%; 5-y OS 37%
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Hypofractionation

  • Rationale
  • Clinical data
  • Points of discussion
  • Future directions
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Which fractionations to use with or without chemo? Any evidence of Dose Limiting Toxicity?

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Which fractionations to use with or without chemo?

  • A. No chemo. British Fractionation: 55 Gy in 20

fractions @ 2.75 Gy/fr.

  • B. Concomitant chemo.
  • SOCCAR Trial: 55 Gy in 20 fr. + CDDP-

VNBx2

  • RADITUX Trial: 66 Gy in 24 fr + Daily CDDP
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Any evidence of Dose Limiting Toxicity?

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Isotoxic dose escaltion 63 Gy 73 Gy in 30 fr. Concurrent CDDP+VNB x 2

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Esophageal MTD = 68 Gy in 30 fr. @ 2.26 Gy/fr

  • Grade 3 esophagitis < 6 %
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Points of Discussion

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Points of Discussion

57 Gy85.5 Gy in 25 daily fractions 57Gy;63Gy;69Gy;75Gy;80Gy No concurrent chemo MTD: <20% risk of severe toxicity

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Points of Discussion

MTD = 63.25 Gy in 25 fractions ! = 70 Gy at 2Gy/fr Grade 4-5 toxicity: 1.8% vs. 31% p=0.0036

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Points of Discussion Inserire appendice A

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Points of Discussion

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Hypofractionation

  • Rationale
  • Clinical data
  • Points of discussion
  • Future directions
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Conclusions:

  • No randomized data on

conventional vs. hypofractionated RT

  • Caution: DLTs exist!
  • Encouraging results are published
  • Future trials are justified
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Thank you for your attention! marco.trovo@cro.it