Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Paola Anselmo,MD | UNKNOWN |
| Michelina Casale,PhD | UNKNOWN |
| Ernesto Maranzano,MD | UNKNOWN |
| Fabio Trippa,MD |
Not provided
Not provided
Not provided
Not provided
This is a prospective, non-randomized, single arm, single institution phase II trial to evaluate the safety and effectiveness of stereoractic ablative radiotherapy (SABR) in selected unresectable newly diagnosed and recurrent locally advanced (LA) non-small cell lung cancer (NSCLC) patients unfit for concurrent chemo-radiotherapy (ChT-RT).
Patients unfit for concurrent ChT-RT but fit for chemotherapy will be enrolled to sequential ChT-SABR; patients unfit for ChT will be enrolled to exclusive SABR.
Current standard of care for fit patients with unresectable LA-NSCLC is concurrent chemo-radiotherapy (ChT-RT) which consists of 6 weeks of radiation and chemotherapy. Unfortunately many LA NSCLC patients, particularly the elderly, are unfit for concurrent ChT-RT because of their poor performance status and co-morbidities. Sequential ChT-RT and/or exclusive RT are options available for patients not suitable for concomitant approaches.
Median progression-free survival among patients receiving concurrent ChT-RT is poor and no more than 15% of cases are alive at 5 years.
This study is evaluating SABR in unresectable LA-NSCLC. Hypofractionated regimens of RT have emerged as a possible approach in LA-NSCLC, not only because prolonged treatments may discourage a proportion of elderly patients (20-30%) who are forced to give up treatment due to distance from the Radiotherapy Centre, but also for radiobiological reasons.
Recent technological advances in RT, first of all stereotactic body radiotherapy (SBRT), have made hypofractionation widely applicable with the possibility to administer few (5 to 8) fractions of high external beam doses to the tumor, sparing the surrounding healthy tissues by a rapid fall of dose outside the target.
LA-NSCLC patients will be discussed at the multidisciplinary lung cancer group and will be judged unfit for surgery and concurrent ChT-RT (e.g. elderly patients and/or large volume of disease and/or cardiovascular comorbidities) but suitable for RT. Neoadjuvant ChT will be evaluated case by case and will be prescribed only in fit patients.
Starting from the standard radical conventionally administered dose for LA-NSCLC (equivalent to at least 54-60 Gy in 27-30 fractions), the investigators decided to prescribe an ablative dose of at least 35-40 Gy in 5 fractions.
The SABR dose will be increased, case by case, respecting the maximum tolerance dose of healthy structures.
The purpose of this study is to explore SABR in the treatment of unresectable LA-NSCLC.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SABR in unresectable LA-NSCLC | Experimental | Patients fit for chemotherapy will be enrolled to sequential chemotherapy-stereotactic ablative radiotherapy (SABR), while patients unfit for chemotherapy will be enrolled to exclusive stereotactic ablative radiotherapy (SABR). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Stereotactic Ablative Radiotherapy in Unresectable Locally Advanced Non-Small Cell Lung Cancer | Radiation | The prescribed dose of stereotactic ablative radiotherapy (SABR) will be of at least 35-40 Gy in 5 fractions. The dose of SABR will be increased, case by case, respecting the maximum tolerance dose of the healthy structures. Participants will SABR once a day for 5 days, Monday through Friday (around 1 week). |
| Measure | Description | Time Frame |
|---|---|---|
| Local control | A lack of progression (i.e., any response and stable disease) of the treated volume according to RECIST and PERCIST. Local recurrence (LR) was defined as tumor progression within the radiation field (95% of the recurrence volume within the original 80% isodose of SABR). Local recurrence-free survival (LR-FS) was defined as the interval between treatment and radiological evidence of LR. | 1 year, 2 years and 3 years |
| Proportion of Participants Experiencing Grade 3 or Higher Toxicities | SABR will be considered safe if no grade (G) 3 or higher toxicities appears. Toxicity, graded according to Common Terminology Criteria for Adverse Events (CTCAE v3.0) will be assessed during SABR and at all follow-up intervals. Toxicity will be recorded as acute when occurred during SABR or within 3 months after completion of treatment. When the time interval will be longer than 3 months, toxicity will be defined late. | 6 months and 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Thoracic nodal-recurrence free survival | The interval between treatment and radiological evidence of any nodal recurrence outside the treated nodes and anyway outside the original isodose of 80% | 1 year, 2 years and 3 years |
| Distant progression free-survival |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Fabio Arcidiacono, MD | Radiotherapy Oncology Centre "S.Maria" Hospital | Principal Investigator |
| Paola Anselmo, MD | Radiotherapy Oncology Centre "S.Maria" Hospital | Principal Investigator |
| Michelina Casale, PhD | Radiotherapy Oncology Centre "S.Maria" Hospital | Principal Investigator |
| Fabio Trippa, MD | Radiotherapy Oncology Centre "S.Maria" Hospital | Study Director |
| Ernesto Maranzano, MD | Radiotherapy Oncology Centre "S.Maria" Hospital | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Radiotherapy Oncology Centre "S.Maria" Hospital | Terni | TR | 05100 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22454424 | Result | Wang S, Wong ML, Hamilton N, Davoren JB, Jahan TM, Walter LC. Impact of age and comorbidity on non-small-cell lung cancer treatment in older veterans. J Clin Oncol. 2012 May 1;30(13):1447-55. doi: 10.1200/JCO.2011.39.5269. Epub 2012 Mar 26. | |
| 20351327 | Result | Auperin A, Le Pechoux C, Rolland E, Curran WJ, Furuse K, Fournel P, Belderbos J, Clamon G, Ulutin HC, Paulus R, Yamanaka T, Bozonnat MC, Uitterhoeve A, Wang X, Stewart L, Arriagada R, Burdett S, Pignon JP. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 2010 May 1;28(13):2181-90. doi: 10.1200/JCO.2009.26.2543. Epub 2010 Mar 29. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| UNKNOWN |
Not provided
Not provided
Not provided
Not provided
Not provided
|
The interval between treatment and radiological evidence of systemic disease progression |
| 1 year, 2 years and 3 years |
| Overall Survival | The overall survival will be calculated from treatment to patient death or last follow-up | 1 year, 2 years, 3 years and 5 years |
| 18718891 | Result | De Ruysscher D, Botterweck A, Dirx M, Pijls-Johannesma M, Wanders R, Hochstenbag M, Dingemans AM, Bootsma G, Geraedts W, Simons J, Pitz C, Lambin P. Eligibility for concurrent chemotherapy and radiotherapy of locally advanced lung cancer patients: a prospective, population-based study. Ann Oncol. 2009 Jan;20(1):98-102. doi: 10.1093/annonc/mdn559. Epub 2008 Aug 20. |
| 24011407 | Result | Sigel K, Lurslurchachai L, Bonomi M, Mhango G, Bergamo C, Kale M, Halm E, Wisnivesky J. Effectiveness of radiation therapy alone for elderly patients with unresected stage III non-small cell lung cancer. Lung Cancer. 2013 Nov;82(2):266-70. doi: 10.1016/j.lungcan.2013.06.011. Epub 2013 Sep 5. |
| 25957184 | Result | Rodrigues G, Choy H, Bradley J, Rosenzweig KE, Bogart J, Curran WJ Jr, Gore E, Langer C, Louie AV, Lutz S, Machtay M, Puri V, Werner-Wasik M, Videtic GMM. Definitive radiation therapy in locally advanced non-small cell lung cancer: Executive summary of an American Society for Radiation Oncology (ASTRO) evidence-based clinical practice guideline. Pract Radiat Oncol. 2015 May-Jun;5(3):141-148. doi: 10.1016/j.prro.2015.02.012. |
| 25601342 | Result | Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, Bogart J, Hu C, Forster K, Magliocco A, Kavadi V, Garces YI, Narayan S, Iyengar P, Robinson C, Wynn RB, Koprowski C, Meng J, Beitler J, Gaur R, Curran W Jr, Choy H. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015 Feb;16(2):187-99. doi: 10.1016/S1470-2045(14)71207-0. Epub 2015 Jan 16. |
| 10661362 | Result | Fowler JF, Chappell R. Non-small cell lung tumors repopulate rapidly during radiation therapy. Int J Radiat Oncol Biol Phys. 2000 Jan 15;46(2):516-7. doi: 10.1016/s0360-3016(99)00364-8. No abstract available. |
| 25846093 | Result | Belderbos J, Walraven I, van Diessen J, Verheij M, de Ruysscher D. Radiotherapy dose and fractionation for stage III NSCLC. Lancet Oncol. 2015 Apr;16(4):e156-7. doi: 10.1016/S1470-2045(15)70121-X. No abstract available. |
| 28109804 | Result | David EA, Daly ME, Li CS, Chiu CL, Cooke DT, Brown LM, Melnikow J, Kelly K, Canter RJ. Increasing Rates of No Treatment in Advanced-Stage Non-Small Cell Lung Cancer Patients: A Propensity-Matched Analysis. J Thorac Oncol. 2017 Mar;12(3):437-445. doi: 10.1016/j.jtho.2016.11.2221. Epub 2017 Jan 18. |
| 25450876 | Result | Kaster TS, Yaremko B, Palma DA, Rodrigues GB. Radical-intent hypofractionated radiotherapy for locally advanced non-small-cell lung cancer: a systematic review of the literature. Clin Lung Cancer. 2015 Mar;16(2):71-9. doi: 10.1016/j.cllc.2014.08.002. Epub 2014 Sep 28. |
| 32275994 | Result | Kong C, Zhu X, Shi M, Wang L, Chen C, Tao H, Jiang N, Yan P, Zhao L, Song X, He X. Survival and Toxicity of Hypofractionated Intensity Modulated Radiation Therapy in 4 Gy Fractions for Unresectable Stage III Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2020 Jul 15;107(4):710-719. doi: 10.1016/j.ijrobp.2020.03.038. Epub 2020 Apr 7. |
| 25746732 | Result | Franks KN, Jain P, Snee MP. Stereotactic ablative body radiotherapy for lung cancer. Clin Oncol (R Coll Radiol). 2015 May;27(5):280-9. doi: 10.1016/j.clon.2015.01.006. Epub 2015 Mar 4. |
| 32822540 | Result | Arcidiacono F, Aristei C, Marchionni A, Italiani M, Fulcheri CPL, Saldi S, Casale M, Ingrosso G, Anselmo P, Maranzano E. Stereotactic body radiotherapy for adrenal oligometastasis in lung cancer patients. Br J Radiol. 2020 Nov 1;93(1115):20200645. doi: 10.1259/bjr.20200645. Epub 2020 Sep 2. |
| 30943123 | Result | Bezjak A, Paulus R, Gaspar LE, Timmerman RD, Straube WL, Ryan WF, Garces YI, Pu AT, Singh AK, Videtic GM, McGarry RC, Iyengar P, Pantarotto JR, Urbanic JJ, Sun AY, Daly ME, Grills IS, Sperduto P, Normolle DP, Bradley JD, Choy H. Safety and Efficacy of a Five-Fraction Stereotactic Body Radiotherapy Schedule for Centrally Located Non-Small-Cell Lung Cancer: NRG Oncology/RTOG 0813 Trial. J Clin Oncol. 2019 May 20;37(15):1316-1325. doi: 10.1200/JCO.18.00622. Epub 2019 Apr 3. |
| 28210143 | Result | Karam SD, Horne ZD, Hong RL, McRae D, Duhamel D, Nasr NM. Hypofractionated stereotactic body radiation therapy for elderly patients with stage IIB-IV nonsmall cell lung cancer who are ineligible for or refuse other treatment modalities. Lung Cancer (Auckl). 2014 Oct 3;5:59-66. doi: 10.2147/LCTT.S66395. eCollection 2014. |
| 27189322 | Result | Schwartz LH, Litiere S, de Vries E, Ford R, Gwyther S, Mandrekar S, Shankar L, Bogaerts J, Chen A, Dancey J, Hayes W, Hodi FS, Hoekstra OS, Huang EP, Lin N, Liu Y, Therasse P, Wolchok JD, Seymour L. RECIST 1.1-Update and clarification: From the RECIST committee. Eur J Cancer. 2016 Jul;62:132-7. doi: 10.1016/j.ejca.2016.03.081. Epub 2016 May 14. |
| 19403881 | Result | Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: Evolving Considerations for PET response criteria in solid tumors. J Nucl Med. 2009 May;50 Suppl 1(Suppl 1):122S-50S. doi: 10.2967/jnumed.108.057307. |
| 20393019 | Result | Nguyen NP, Bishop M, Borok TJ, Welsh J, Hamilton R, Cohen D, Nguyen LM, Vincent VH. Pattern of failure following chemoradiation for locally advanced non-small cell lung cancer: potential role for stereotactic body radiotherapy. Anticancer Res. 2010 Mar;30(3):953-61. |
| 33476803 | Result | Faivre-Finn C, Vicente D, Kurata T, Planchard D, Paz-Ares L, Vansteenkiste JF, Spigel DR, Garassino MC, Reck M, Senan S, Naidoo J, Rimner A, Wu YL, Gray JE, Ozguroglu M, Lee KH, Cho BC, Kato T, de Wit M, Newton M, Wang L, Thiyagarajah P, Antonia SJ. Four-Year Survival With Durvalumab After Chemoradiotherapy in Stage III NSCLC-an Update From the PACIFIC Trial. J Thorac Oncol. 2021 May;16(5):860-867. doi: 10.1016/j.jtho.2020.12.015. Epub 2021 Jan 19. |
| 30095228 | Result | Ahmed N, Hasan S, Schumacher L, Colonias A, Wegner RE. Stereotactic body radiotherapy for central lung tumors: Finding the balance between safety and efficacy in the "no fly" zone. Thorac Cancer. 2018 Oct;9(10):1211-1214. doi: 10.1111/1759-7714.12764. Epub 2018 Aug 10. |
| 30496842 | Result | Nguyen KNB, Hause DJ, Novak J, Monjazeb AM, Daly ME. Tumor Control and Toxicity after SBRT for Ultracentral, Central, and Paramediastinal Lung Tumors. Pract Radiat Oncol. 2019 Mar;9(2):e196-e202. doi: 10.1016/j.prro.2018.11.005. Epub 2018 Nov 26. |
| 27013408 | Result | Tekatli H, Haasbeek N, Dahele M, De Haan P, Verbakel W, Bongers E, Hashemi S, Nossent E, Spoelstra F, de Langen AJ, Slotman B, Senan S. Outcomes of Hypofractionated High-Dose Radiotherapy in Poor-Risk Patients with "Ultracentral" Non-Small Cell Lung Cancer. J Thorac Oncol. 2016 Jul;11(7):1081-9. doi: 10.1016/j.jtho.2016.03.008. Epub 2016 Mar 21. |
| 36288758 | Derived | Arcidiacono F, Anselmo P, Casale M, Zannori C, Ragusa M, Mancioli F, Marchetti G, Loreti F, Italiani M, Bracarda S, Maranzano E, Trippa F. STereotactic Ablative RadioTherapy in NEWly Diagnosed and Recurrent Locally Advanced Non-Small Cell Lung Cancer Patients Unfit for ConcurrEnt RAdio-Chemotherapy: Early Analysis of the START-NEW-ERA Non-Randomised Phase II Trial. Int J Radiat Oncol Biol Phys. 2023 Mar 15;115(4):886-896. doi: 10.1016/j.ijrobp.2022.10.025. Epub 2022 Oct 24. |