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Nardone V, Bruni A, Franceschini D, Marini B, Vagge S, Ciammella P, Sepulcri M, Cappelli A, D'Angelo E, De Marco G, Angrisani A, Manetta M, Scricciolo M, Guida C, Aiello D, Borghetti P, Cappabianca S. Adjuvant modern radiotherapy in resected pN2 NSCLC patients: results from a multicentre retrospective analysis on acute and late toxicity on behalf of AIRO thoracic oncology study group: the RAC-TAC study. LA RADIOLOGIA MEDICA 2024; 129:1700-1709. [PMID: 39215945 PMCID: PMC11554814 DOI: 10.1007/s11547-024-01885-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Accepted: 08/21/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND Recently, the PORT-C and LUNG-ART trials, which evaluated the role of postoperative radiation therapy (PORT), have significantly altered the treatment landscape for NSCLC pN2 patients who previously underwent surgery. In response, the Italian Association of Radiotherapy and Oncology Thoracic Oncology study group has initiated an observational multicenter trial to assess both acute and late toxicities of PORT in pN2 NSCLC patients treated with modern techniques. METHODS Data on NSCLC patients submitted to PORT after radical surgery treated between 2015 and 2020 in six Italian Centers were collected. Heart, lung, and esophageal acute and late toxicities have been retrospectively analyzed and related to radiation therapy dosimetric parameters. Furthermore, loco-regional control, distant metastasis and overall survival have been analyzed. RESULTS A total of 212 patients with a median age of 68 years from six different centers were included in this analysis (142 males and 70 females). Prior to undergoing PORT, 96 patients (45.8%) had a history of heart disease, 110 patients (51.9%) had hypertension, and 51 patients (24%) had COPD. Acute toxicity was observed in 147 patients (69.3%), with lung toxicity occurring in 93 patients (G1 in 70 patients, G2 in 17 patients, and G3 in 4 patients), esophageal toxicity in 114 patients (G1 in 89 patients, G2 in 23 patients, and G3 in 1 patient), and cardiac toxicity in 4 patients (G1 in 2 patients and G3 in 2 patients). Late side effects were found in 60 patients (28.3%), predominantly involving the lungs (51 patients: 32 G1, 11 G2, and 1 G3) and the esophagus (11 patients: 8 G1 and 3 G2), with no reported late cardiac side effects. Various clinical and dosimetric parameters were found to correlate with both acute and chronic toxicities. Over a median follow-up period of 54 months, 48 patients (22.6%) showed locoregional disease relapse, 106 patients (50%) developed distant metastases, and 66 patients (31.1%) died. CONCLUSIONS RAC-TAC retrospective multicentric study showed the low toxicity of PORT when advanced technology is used. At the same time, it's noteworthy to underline that 50% of the patients develop distant recurrences in the follow up.
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Affiliation(s)
- Valerio Nardone
- Department of Precision Medicine, University of Campania "L. Vanvitelli", Naples, Italy.
| | - Alessio Bruni
- Radiotherapy Unit, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy
| | - Davide Franceschini
- Department of Radiotherapy and Radiosurgery, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Beatrice Marini
- Department of Radiotherapy and Radiosurgery, IRCCS Humanitas Research Hospital, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Stefano Vagge
- Radiation Oncology Department, E.O. Ospedali Galliera, Genoa, Italy
| | - Patrizia Ciammella
- Radiation Oncology Unit, Azienda USL-IRCCS Di Reggio Emilia, 42123, Reggio Emilia, Italy
| | - Matteo Sepulcri
- Radiotherapy, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Anna Cappelli
- Radiotherapy Unit, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy
- Radiotherapy Unit, University Hospital of Modena, Modena, Italy
| | - Elisa D'Angelo
- Radiation Oncology Department, Bellaria Hospital, AUSL of Bologna, Bologna, Italy
| | - Giuseppina De Marco
- Department of Precision Medicine, University of Campania "L. Vanvitelli", Naples, Italy
| | - Antonio Angrisani
- Department of Precision Medicine, University of Campania "L. Vanvitelli", Naples, Italy
- Radiation Oncology, Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland
| | - Mattia Manetta
- Radiation Oncology Department, ASST Spedali Civili and University of Brescia, Brescia, Italy
| | | | - Cesare Guida
- Radiotherapy Unit, ASL Napoli 1 Centro, Ospedale del Mare, Naples, Italy
| | - Dario Aiello
- Radiation Oncology, Casa Di Cura Macchiarella, Palermo, Italy
| | - Paolo Borghetti
- Radiation Oncology Department, ASST Spedali Civili and University of Brescia, Brescia, Italy
| | - Salvatore Cappabianca
- Department of Precision Medicine, University of Campania "L. Vanvitelli", Naples, Italy
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Iocolano M, Yegya-Raman N, Friedes C, Wang X, Kegelman T, Lee SH, Duan L, Li B, Levin WP, Cengel KA, Konski A, Langer CJ, Cohen RB, Sun L, Aggarwal C, Doucette A, Xiao Y, Kevin Teo BK, O'Reilly S, Zou W, Bradley JD, Simone CB, Feigenberg SJ. Acute hospitalizations after proton therapy versus intensity-modulated radiotherapy for locally advanced non-small cell lung cancer in the durvalumab era. Cancer 2024; 130:2031-2041. [PMID: 38294959 DOI: 10.1002/cncr.35230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 11/25/2023] [Accepted: 12/05/2023] [Indexed: 02/02/2024]
Abstract
INTRODUCTION It was hypothesized that use of proton beam therapy (PBT) in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiation and consolidative immune checkpoint inhibition is associated with fewer unplanned hospitalizations compared with intensity-modulated radiotherapy (IMRT). METHODS Patients with locally advanced non-small cell lung cancer treated between October 2017 and December 2021 with concurrent chemoradiation with either IMRT or PBT ± consolidative immune checkpoint inhibition were retrospectively identified. Logistic regression was used to assess the association of radiation therapy technique with 90-day hospitalization and grade 3 (G3+) lymphopenia. Competing risk regression was used to compare G3+ pneumonitis, G3+ esophagitis, and G3+ cardiac events. Kaplan-Meier method was used for progression-free survival and overall survival. Inverse probability treatment weighting was applied to adjust for differences in PBT and IMRT groups. RESULTS Of 316 patients, 117 (37%) received PBT and 199 (63%) received IMRT. The PBT group was older (p < .001) and had higher Charlson Comorbidity Index scores (p = .02). The PBT group received a lower mean heart dose (p < .0001), left anterior descending artery V15 Gy (p = .001), mean lung dose (p = .008), and effective dose to immune circulating cells (p < .001). On inverse probability treatment weighting analysis, PBT was associated with fewer unplanned hospitalizations (adjusted odds ratio, 0.55; 95% CI, 0.38-0.81; p = .002) and less G3+ lymphopenia (adjusted odds ratio, 0.55; 95% CI, 0.37-0.81; p = .003). There was no difference in other G3+ toxicities, progression-free survival, or overall survival. CONCLUSIONS PBT is associated with fewer unplanned hospitalizations, lower effective dose to immune circulating cells and less G3+ lymphopenia compared with IMRT. Minimizing dose to lymphocytes may be warranted, but prospective data are needed.
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Affiliation(s)
- Michelle Iocolano
- Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Nikhil Yegya-Raman
- Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Cole Friedes
- Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Xingmei Wang
- Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Timothy Kegelman
- Department of Radiation Oncology, Delaware Radiation Oncology Associates, Christiana Care Health Systems, Newark, Delaware, USA
| | - Sang Ho Lee
- Department of Radiation Oncology, Division of Physics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Lian Duan
- Department of Radiation Oncology, Division of Physics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
- Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Bolin Li
- Department of Radiation Oncology, Division of Physics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - William P Levin
- Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Keith A Cengel
- Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Andre Konski
- Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
- Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Corey J Langer
- Division of Hematology/Oncology University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Roger B Cohen
- Division of Hematology/Oncology University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Lova Sun
- Division of Hematology/Oncology University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Charu Aggarwal
- Division of Hematology/Oncology University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Abigail Doucette
- Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Ying Xiao
- Department of Radiation Oncology, Division of Physics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Boon-Keng Kevin Teo
- Department of Radiation Oncology, Division of Physics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Shannon O'Reilly
- Department of Radiation Oncology, Division of Physics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Wei Zou
- Department of Radiation Oncology, Division of Physics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Jeffrey D Bradley
- Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | | | - Steven J Feigenberg
- Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
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Jiang L, Meng X. Is there role of adjuvant radiotherapy after complete resection of locally advanced nonsmall cell lung cancer? Curr Opin Oncol 2024; 36:44-50. [PMID: 37865829 DOI: 10.1097/cco.0000000000001004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2023]
Abstract
PURPOSE OF REVIEW This review aims to provide a timely and relevant overview of the role of postoperative radiotherapy (PORT) in completely resected stage IIIA-N2 nonsmall cell lung cancer (NSCLC). Given the controversy surrounding the use of PORT and the emergence of advanced radiation techniques and therapies, this review provides valuable insight into current and potential treatment strategies. RECENT FINDINGS The Lung ART and PORT-C trials have provided valuable insights into the efficacy of PORT in stage IIIA-N2 NSCLC. While the results have been mixed, studies have shown that advanced radiation techniques, such as intensity-modulated radiotherapy (IMRT) and proton therapy, can reduce cardiopulmonary toxicities associated with PORT. Molecular targeted therapies and immunotherapies have also shown potential in improving NSCLC treatment outcomes. SUMMARY The role of radiotherapy becomes smaller and smaller in new era. However, it is too early to abolish radiotherapy for all the patients after complete resection of locally advanced NSCLC. Nowadays, it is recommended to adopt individualized treatment approaches guided by multidisciplinary team consultations. The integration of IMRT, proton therapy, and emerging therapies offers the potential to enhance treatment efficacy while minimizing toxicity. Further research is needed to optimize the use of PORT and explore the method to identify the patients who can really benefit from PORT.
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Affiliation(s)
- Liyang Jiang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
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Choi JI, Simone CB, Lozano A, Frank SJ. Advances and Challenges in Conducting Clinical Trials With Proton Beam Therapy. Semin Radiat Oncol 2023; 33:407-415. [PMID: 37684070 PMCID: PMC10503212 DOI: 10.1016/j.semradonc.2023.06.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/10/2023]
Abstract
Advances in proton therapy have garnered much attention and speculation in recent years as the indications for proton therapy have grown beyond pediatric, prostate, spine, and ocular tumors. To achieve and maintain consistent access to this cancer treatment and to ensure the future viability and availability of proton centers in the United States, a call for evidence has been heard and answered by proton radiation oncologists. Answers provided in this review include the evolution of proton therapy research, rationale for proton clinical trial design, challenges in and barriers to the conduct of proton therapy research, and other unique considerations for the study of proton therapy.
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Affiliation(s)
- J Isabelle Choi
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.; New York Proton Center, New York, NY..
| | - Charles B Simone
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.; New York Proton Center, New York, NY
| | - Alicia Lozano
- Center for Biostatistics and Health Data Science, Department of Statistics, Virginia Tech, Roanoke, VA
| | - Steven J Frank
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
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Cinicola J, Mamidanna S, Yegya-Raman N, Spencer K, Deek MP, Jabbour SK. A Review of Advances in Radiotherapy in the Setting of Esophageal Cancers. Surg Oncol Clin N Am 2023; 32:433-459. [PMID: 37182986 DOI: 10.1016/j.soc.2023.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/16/2023]
Abstract
Esophageal cancer is the eighth most common cancer worldwide and is the sixth most common cause of cancer-related mortality. The paradigm has shifted to include a multimodality approach with surgery, chemotherapy, targeted therapy (including immunotherapy), and radiation therapy. Advances in radiotherapy through techniques such as intensity modulated radiotherapy and proton beam therapy have allowed for the more dose homogeneity and improved organ sparing. In addition, recent studies of targeted therapies and predictive approaches in patients with locally advanced disease provide clinicians with new approaches to modify multimodality treatment to improve clinical outcomes.
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Affiliation(s)
- Joshua Cinicola
- Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA
| | - Swati Mamidanna
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson School of Medicine, Rutgers University, New Brunswick, NJ, USA
| | - Nikhil Yegya-Raman
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA
| | - Kristen Spencer
- New York Langone Perlmutter Cancer Center, New York, NY, USA
| | - Matthew P Deek
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson School of Medicine, Rutgers University, New Brunswick, NJ, USA
| | - Salma K Jabbour
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson School of Medicine, Rutgers University, New Brunswick, NJ, USA.
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Simone CB, Bradley J, Chen AB, Daly ME, Louie AV, Robinson CG, Videtic GMM, Rodrigues G. ASTRO Radiation Therapy Summary of the ASCO Guideline on Management of Stage III Non-Small Cell Lung Cancer. Pract Radiat Oncol 2023; 13:195-202. [PMID: 37080641 DOI: 10.1016/j.prro.2023.01.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 01/10/2023] [Accepted: 01/12/2023] [Indexed: 04/22/2023]
Abstract
PURPOSE To develop a radiation therapy summary of recommendations on the management of locally advanced non-small cell lung cancer (NSCLC) based on the Management of Stage III Non-Small Cell Lung Cancer: American Society of Clinical Oncology Guideline, which was endorsed by the American Society for Radiation Oncology (ASTRO). METHODS The American Society of Clinical Oncology, ASTRO, and the American College of Chest Physicians convened a multidisciplinary panel to develop a guideline based on a systematic review of the literature and a formal consensus process, that has been separately published. A new panel consisting of radiation oncologists from the original guideline as well as additional ASTRO members was formed to provide further guidance to the radiation oncology community. A total of 127 articles met the eligibility criteria to answer 5 clinical questions. This summary focuses on the 3 radiation therapy questions (neoadjuvant, adjuvant, and unresectable settings). RESULTS Radiation-specific recommendations are summarized with additional relevant commentary on specific questions regarding the management of preoperative radiation, postoperative radiation, and combined chemoradiation. CONCLUSIONS Patients with stage III NSCLC who are planned for surgical resection, should receive either neoadjuvant chemotherapy or chemoradiation. The addition of neoadjuvant treatment is particularly important in patients planned for surgery in the N2 or superior sulcus settings. Postoperatively, patients who did not receive neoadjuvant chemotherapy should be offered adjuvant chemotherapy. The use of postoperative radiation for completely resected N2 disease is not routinely recommended. Unresectable patients with stage III NSCLC should ideally be managed with combined concurrent chemoradiation using a platinum-based doublet with a standard radiation dose of 60 Gy followed by consolidation durvalumab in patients without progression after initial therapy. Patients who cannot tolerate a concurrent chemoradiation approach can be managed either by sequential chemotherapy followed by radiation or by dose-escalated or hypofractionated radiation alone.
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Affiliation(s)
- Charles B Simone
- Department of Radiation Oncology, New York Proton Center, New York, New York
| | - Jeffrey Bradley
- Department of Radiation Oncology, Emory University School of Medicine, Atlanta, Georgia
| | - Aileen B Chen
- Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Megan E Daly
- Department of Radiation Oncology, University of California Davis Comprehensive Cancer Center, Sacramento, California
| | - Alexander V Louie
- Department of Radiation Oncology, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada
| | - Clifford G Robinson
- Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri
| | - Gregory M M Videtic
- Department of Radiation Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio
| | - George Rodrigues
- Department of Radiation Oncology, London Health Sciences Cancer, London, Ontario, Canada.
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Chen Z, Dominello MM, Joiner MC, Burmeister JW. Proton versus photon radiation therapy: A clinical review. Front Oncol 2023; 13:1133909. [PMID: 37064131 PMCID: PMC10091462 DOI: 10.3389/fonc.2023.1133909] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Accepted: 03/13/2023] [Indexed: 03/31/2023] Open
Abstract
While proton radiation therapy offers substantially better dose distribution characteristics than photon radiation therapy in certain clinical applications, data demonstrating a quantifiable clinical advantage is still needed for many treatment sites. Unfortunately, the number of patients treated with proton radiation therapy is still comparatively small, in some part due to the lack of evidence of clear benefits over lower-cost photon-based treatments. This review is designed to present the comparative clinical outcomes between proton and photon therapies, and to provide an overview of the current state of knowledge regarding the effectiveness of proton radiation therapy.
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Affiliation(s)
- Zhe Chen
- School of Medicine, Wayne State University, Detroit, MI, United States
- *Correspondence: Zhe Chen,
| | - Michael M. Dominello
- Karmanos Cancer Institute, Department of Oncology, Wayne State University School of Medicine, Detroit, MI, United States
| | - Michael C. Joiner
- Karmanos Cancer Institute, Department of Oncology, Wayne State University School of Medicine, Detroit, MI, United States
| | - Jay W. Burmeister
- Karmanos Cancer Institute, Department of Oncology, Wayne State University School of Medicine, Detroit, MI, United States
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Kim KN, Heintz J, Yegya-Raman N, Cohen R, Kegelman T, Cengel K, Marmarelis M, Sun L, Langer C, Aggarwal C, Singh A, Singhal S, Kucharczuk J, Robinson K, Feigenberg S. Toxicities and Deaths From Intercurrent Disease Following Contemporary Postoperative Radiotherapy in Resected Non-Small-Cell Lung Cancer. Clin Lung Cancer 2023; 24:e78-e86. [PMID: 36628846 DOI: 10.1016/j.cllc.2022.12.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Revised: 12/04/2022] [Accepted: 12/16/2022] [Indexed: 12/26/2022]
Abstract
INTRODUCTION The role of postoperative radiotherapy (PORT) in patients with resected locally advanced non-small-cell lung cancer (NSCLC) remains controversial due to the radiation techniques used in randomized trials. We conducted a retrospective cohort study evaluating contemporary PORT techniques to evaluate the safety of PORT and risk of death from intercurrent disease . MATERIALS AND METHODS We analyzed consecutive patients with NSCLC treated in a single center that underwent PORT for pN2 disease and/or positive margin, with 3-dimensional conformal radiotherapy (3DRT), intensity modulated radiotherapy , or proton RT (PRT), between 2008 and 2019. Clinical details were collected including intercurrent deaths, defined as death without cancer recurrence. Kaplan-Meier and Cox-Proportional Hazards Models were used. RESULTS Of 119 patients, 21 (17.6%) received 3DRT, 47 (39.5%) intensity modulated radiotherapy, and 51 (42.9%) PRT. Median follow-up was 40 months (range 8-136) and median RT dose was 5040cGy. Most patients (65.5%) received sequential adjuvant chemoRT; 18.5% received concurrent chemoRT. The rate of grade 3 toxicities was 9.2%. There were 13 (10.9%) deaths from intercurrent diseases, including 6 from second primary cancers and 2 from cardiopulmonary diseases. There were 2 additional deaths from cardiopulmonary disease in patients with cancer progression at time of death. Mean, V5Gy, V30Gy heart doses and mean lung doses were significantly lower with PRT. Three-year OS and disease-free-survival were 70.1% and 49.9%. CONCLUSION PORT using contemporary techniques was well tolerated with acceptable toxicity and low rates of intercurrent deaths. Proton therapy significantly reduced heart and lung doses, but radiotherapy modality was not associated with differences in intercurrent disease.
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Affiliation(s)
- Kristine N Kim
- Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
| | - Jonathan Heintz
- Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Nikhil Yegya-Raman
- Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Roger Cohen
- Division of Hematology Oncology, Department of Internal Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Timothy Kegelman
- Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Keith Cengel
- Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Melina Marmarelis
- Division of Hematology Oncology, Department of Internal Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Lova Sun
- Division of Hematology Oncology, Department of Internal Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Corey Langer
- Division of Hematology Oncology, Department of Internal Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Charu Aggarwal
- Division of Hematology Oncology, Department of Internal Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Aditi Singh
- Division of Hematology Oncology, Department of Internal Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Sunil Singhal
- Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - John Kucharczuk
- Division of Thoracic Surgery, Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Kyle Robinson
- Division of Hematology Oncology, Department of Internal Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Steven Feigenberg
- Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
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Yu B, Jun Ma S, Waldman O, Dunne-Jaffe C, Chatterjee U, Turecki L, Gill J, Yendamuri K, Iovoli A, Farrugia M, Singh AK. Trends in Postoperative Intensity-Modulated Radiation Therapy Use and Its Association With Survival Among Patients With Incompletely Resected Non-Small Cell Lung Cancer. JAMA Netw Open 2022; 5:e2230704. [PMID: 36074462 PMCID: PMC9459658 DOI: 10.1001/jamanetworkopen.2022.30704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Accepted: 07/22/2022] [Indexed: 11/14/2022] Open
Abstract
IMPORTANCE National guidelines allow consideration of postoperative radiation therapy (PORT) among patients with incompletely resected non-small cell lung cancer (NSCLC). However, there is a paucity of prospective data because recently completed trials excluded patients with positive surgical margins. In addition, unlike for locally advanced NSCLC, the role of intensity-modulated radiation therapy (IMRT) for PORT remains unclear. OBJECTIVE To evaluate trends of IMRT use for PORT in the US and the association of IMRT with survival outcomes among patients with incompletely resected NSCLC. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study used data from the National Cancer Database for patients diagnosed between January 2004 and December 2019 with incompletely resected NSCLC who underwent upfront surgery with positive surgical margins followed by PORT. EXPOSURES IMRT vs 3D conformal radiation therapy (3DCRT) for PORT. MAIN OUTCOMES AND MEASURES The main outcome was overall survival. Multivariable Cox proportional hazards regression assessed the association of IMRT vs 3DCRT with overall survival. Multivariable logistic regression identified variables associated with IMRT. Propensity score matching (1:1) was performed based on variables of interest. RESULTS A total of 4483 patients (2439 men [54.4%]; median age, 67 years [IQR, 60-73 years]) were included in the analysis. Of those, 2116 (47.2%) underwent 3DCRT and 2367 (52.8%) underwent IMRT. Median follow-up was 48.5 months (IQR, 31.1-77.2 months). The proportion of patients who underwent IMRT increased from 14.3% (13 of 91 patients) in 2004 to 70.7% (33 of 471 patients) in 2019 (P < .001). IMRT was associated with improved overall survival compared with 3DCRT (adjusted hazard ratio, 0.84; 95% CI, 0.78-0.91; P < .001). Similar findings were observed for 1463 propensity score-matched pairs; IMRT was associated with improved 5-year overall survival compared with 3DCRT (37.3% vs 32.2%; hazard ratio, 0.88; 95% CI, 0.80-0.96; P = .003). IMRT use was associated with receipt of treatment at an academic facility (adjusted odds ratio [aOR], 1.15; 95% CI, 1.00-1.33; P = .049), having T4 stage tumors (aOR, 1.50; 95% CI, 1.13-1.99; P = .005) or N2 or N3 stage tumors (aOR, 1.25; 95% CI, 1.04-1.51; P = .02), and receipt of pneumonectomy (aOR, 1.35; 95% CI, 1.02-1.80; P = .04). CONCLUSION AND RELEVANCE This cohort study found that use of IMRT for PORT among patients with incompletely resected NSCLC increased in the US from 2004 to 2019 and was associated with improved survival compared with 3DCRT. Further studies are warranted to investigate the role of different radiation therapy techniques for PORT.
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Affiliation(s)
- Brian Yu
- Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo
| | - Sung Jun Ma
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York
| | - Olivia Waldman
- Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo
| | - Cynthia Dunne-Jaffe
- Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo
| | - Udit Chatterjee
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York
| | - Lauren Turecki
- Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo
| | - Jasmin Gill
- University at Buffalo, The State University of New York, Buffalo
| | - Keerti Yendamuri
- University at Buffalo, The State University of New York, Buffalo
| | - Austin Iovoli
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York
| | - Mark Farrugia
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York
| | - Anurag K. Singh
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York
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10
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Amstutz F, Fabiano S, Marc L, Weber DC, Lomax AJ, Unkelbach J, Zhang Y. Combined proton-photon therapy for non-small cell lung cancer. Med Phys 2022; 49:5374-5386. [PMID: 35561077 PMCID: PMC9544482 DOI: 10.1002/mp.15715] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 04/18/2022] [Accepted: 05/08/2022] [Indexed: 11/10/2022] Open
Abstract
PURPOSE Advanced non-small cell lung cancer (NSCLC) is still a challenging indication for conventional photon radiotherapy. Proton therapy has the potential to improve outcomes, but proton treatment slots remain a limited resource despite an increasing number of proton therapy facilities. This work investigates the potential benefits of optimally combined proton-photon therapy delivered using a fixed horizontal proton beam line in combination with a photon Linac, which could increase accessibility to proton therapy for such a patient cohort. MATERIALS AND METHODS A treatment planning study has been conducted on a patient cohort of seven advanced NSCLC patients. Each patient had a planning CT and multiple repeated CTs from three different days and for different breath-holds on each day. Treatment plans for combined proton-photon therapy (CPPT) were calculated for individual patients by optimizing the combined cumulative dose on the initial planning CT only (non-adapted) as well as on each daily CT respectively (adapted). The impact of inter-fractional changes and/or breath-hold variability was then assessed on the repeat breath-hold CTs. Results were compared to plans for IMRT or IMPT alone, as well as against combined treatments assuming a proton gantry. Plan quality was assessed in terms of dosimetric, robustness and NTCP metrics. RESULTS Combined treatment plans improved plan quality compared to IMRT treatments, especially in regard to reductions of low and medium doses to organs at risk (OARs), which translated into lower NTCP estimates for three side effects. For most patients, combined treatments achieved results close to IMPT-only plans. Inter-fractional changes impact mainly the target coverage of combined and IMPT treatments, while OARs doses were less affected by these changes. With plan adaptation however, target coverage of combined treatments remained high even when taking variability between breath-holds into account. CONCLUSIONS Optimally combined proton-photon plans improve treatment plan quality compared to IMRT only, potentially reducing the risk of toxicity while also allowing to potentially increase accessibility to proton therapy for NSCLC patients. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Florian Amstutz
- Center for Proton Therapy, Paul Scherrer Institute, Villigen, Switzerland.,Department of Physics, ETH Zurich, Zurich, Switzerland
| | - Silvia Fabiano
- Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland
| | - Louise Marc
- Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland
| | - Damien C Weber
- Center for Proton Therapy, Paul Scherrer Institute, Villigen, Switzerland.,Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland.,Department of Radiation Oncology, University Hospital Bern, Bern, Switzerland
| | - Antony J Lomax
- Center for Proton Therapy, Paul Scherrer Institute, Villigen, Switzerland.,Department of Physics, ETH Zurich, Zurich, Switzerland
| | - Jan Unkelbach
- Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland
| | - Ye Zhang
- Center for Proton Therapy, Paul Scherrer Institute, Villigen, Switzerland
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11
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Algranati C, Strigari L. Imaging Strategies in Proton Therapy for Thoracic Tumors: A Mini Review. Front Oncol 2022; 12:833364. [PMID: 35515119 PMCID: PMC9063639 DOI: 10.3389/fonc.2022.833364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Accepted: 02/09/2022] [Indexed: 11/13/2022] Open
Abstract
Proton beam therapy (PBT) is often more attractive for its high gradient dose distributions than other treatment modalities with external photon beams. However, in thoracic lesions treated particularly with pencil beam scanning (PBS) proton beams, several dosimetric issues are addressed. The PBS approach may lead to large hot or cold spots in dose distributions delivered to the patients, potentially affecting the tumor control and/or increasing normal tissue side effects. This delivery method particularly benefits image-guided approaches. Our paper aims at reviewing imaging strategies and their technological trends for PBT in thoracic lesions. The focus is on the use of imaging strategies in simulation, planning, positioning, adaptation, monitoring, and delivery of treatment and how changes in the anatomy of thoracic tumors are handled with the available tools and devices in PBT. Starting from bibliographic research over the past 5 years, retrieving 174 papers, major key questions, and implemented solutions were identified and discussed; the results aggregated and presented following the methodology of analysis of expert interviews.
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Affiliation(s)
- Carlo Algranati
- Proton Therapy Department, Azienda Provinciale per i Servizi Sanitari (APSS), Trento, Italy
- Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale (DIMES), University of Bologna, Bologna, Italy
| | - Lidia Strigari
- Department of Medical Physics, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- *Correspondence: Lidia Strigari,
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12
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Role of Adjuvant Radiotherapy in Non-Small Cell Lung Cancer-A Review. Cancers (Basel) 2022; 14:cancers14071617. [PMID: 35406388 PMCID: PMC8997169 DOI: 10.3390/cancers14071617] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Revised: 03/14/2022] [Accepted: 03/19/2022] [Indexed: 11/17/2022] Open
Abstract
Simple Summary The role of postoperative radiotherapy (PORT) in completely resected non-small cell lung cancer (NSCLC) with ipsilateral mediastinal lymph node involvement (pN2) is controversial. The aim of our review was to study the literature relating to PORT for completely resected NSCLC patients with pN2 involvement. The Lung ART and PORT-C trials indicate better locoregional control with PORT, but this has not yet translated into survival benefits. Given the conflicting results, guidelines do not recommend the use of PORT routinely. Future research should focus on identifying subgroups of patients who might benefit from PORT. Abstract Background: For patients with completely resected non-small cell lung cancer (NSCLC) with ipsilateral mediastinal lymph node involvement (pN2), the administration of adjuvant chemotherapy is the standard of care. The role of postoperative radiation therapy (PORT) is controversial. Methods: We describe the current literature focusing on the role of PORT in completely resected NSCLC patients with pN2 involvement and reflect on its role in current guidelines. Results: Based on the results of the recent Lung ART and PORT-C trials, the authors conclude that PORT cannot be generally recommended for all resected pN2 NSCLC patients. A substantial decrease in the locoregional relapse rate without translating into a survival benefit suggests that some patients with risk factors might benefit from PORT. This must be balanced against the risk of cardiopulmonary toxicity with potentially associated mortality. Lung ART has already changed the decision making for the use of PORT in daily practice for many European lung cancer experts, with lower rates of recommendations for PORT overall. Conclusions: PORT is still used, albeit decreasingly, for completely resected NSCLC with pN2 involvement. High-level evidence for its routine use is lacking. Further analyses are required to identify patients who would potentially benefit from PORT.
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Serrano J, Crespo PC, Taboada B, Gonzalez AA, García RG, Caamaño AG, Reyes JCT, Mielgo-Rubio X, Couñago F. Postoperative radiotherapy in resected non-small cell lung cancer: The never-ending story. World J Clin Oncol 2021; 12:833-844. [PMID: 34733608 PMCID: PMC8546654 DOI: 10.5306/wjco.v12.i10.833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 06/20/2021] [Accepted: 09/14/2021] [Indexed: 02/06/2023] Open
Abstract
This manuscript collects in a joint and orderly manner the existing evidence at the present time about postoperative treatment with radiotherapy in non-small cell lung cancer. It also systematically reviews the current evidence, the international recommendations in the most relevant guidelines, the most controversial aspects in clinical and pathological staging, the specific technical aspects of radiotherapy treatment, and also collects all the potential risk factors that have been postulated as significant in the prognosis of these patients, evaluating the possibility of segmenting a particularly sensitive subpopulation with a high risk of relapse on which an adjuvant treatment with radiotherapy could have an impact on their clinical evolution. Finally, currently active trials that aspire to provide more evidence on this topic are reviewed.
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Affiliation(s)
- Javier Serrano
- Department of Radiation Therapy, Clinica Universidad de Navarra, Madrid 28027, Spain
| | - Patricia Calvo Crespo
- Department of Radiation Oncology, Hospital Clínico Universitario Santiago de Compostela, Santiago de Compostela 15706, Spain
| | - Begoña Taboada
- Department of Radiation Oncology, Hospital Clínico Universitario Santiago de Compostela, Santiago de Compostela 15706, Spain
| | | | - Rafael Garcia García
- Department of Radiation Oncology, Hospital Ruber Internacional, Madrid 28034, Spain
| | - Antonio Gomez Caamaño
- Department of Radiation Oncology, Hospital Clínico Universitario Santiago de Compostela, A Coruña 15706, Spain
| | | | - Xabier Mielgo-Rubio
- Department of Medical Oncology, Hospital Universitario Fundación Alcorcón, Madrid 28922, Spain
| | - Felipe Couñago
- Department of Radiation Oncology, Hospital Universitario Quirónsalud Madrid, Hospital La Luz, Universidad Europea de Madrid, Madrid 28223, Spain
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14
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Dosimetry, Efficacy, Safety, and Cost-Effectiveness of Proton Therapy for Non-Small Cell Lung Cancer. Cancers (Basel) 2021; 13:cancers13184545. [PMID: 34572772 PMCID: PMC8465697 DOI: 10.3390/cancers13184545] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Revised: 09/04/2021] [Accepted: 09/07/2021] [Indexed: 12/24/2022] Open
Abstract
Non-small cell lung cancer (NSCLC) is the most common malignancy which requires radiotherapy (RT) as an important part of its multimodality treatment. With the advent of the novel irradiation technique, the clinical outcome of NSCLC patients who receive RT has been dramatically improved. The emergence of proton therapy, which allows for a sharper dose of build-up and drop-off compared to photon therapy, has potentially improved clinical outcomes of NSCLC. Dosimetry studies have indicated that proton therapy can significantly reduce the doses for normal organs, especially the lung, heart, and esophagus while maintaining similar robust target volume coverage in both early and advanced NSCLC compared with photon therapy. However, to date, most studies have been single-arm and concluded no significant changes in the efficacy for early-stage NSCLC by proton therapy over stereotactic body radiation therapy (SBRT). The results of proton therapy for advanced NSCLC in these studies were promising, with improved clinical outcomes and reduced toxicities compared with historical photon therapy data. However, these studies were also mainly single-arm and lacked a direct comparison between the two therapies. Currently, there is much emerging evidence focusing on dosimetry, efficacy, safety, and cost-effectiveness of proton therapy for NSCLC that has been published, however, a comprehensive review comparing these therapies is, to date, lacking. Thus, this review focuses on these aspects of proton therapy for NSCLC.
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