The Multidisciplinary Approach in Stage III Non-Small Cell Lung Cancer over Ten Years: From Radiation Therapy Optimisation to Innovative Systemic Treatments
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Immunohistochemistry for PD-L1, ALK and ROS-1
2.2. Molecular Investigation of EGFR Mutations
2.3. Statistical Analysis
3. Results
3.1. Clinico-Pathological Characteristics
3.2. Therapeutic Pathways and Treatment Responses
3.3. Treatment Outcomes
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Trial | Regimen | Median OS (Months) | 2 y OS | 5 y OS |
---|---|---|---|---|
Meta-Analysis 2006 | ||||
RT Alone | - | 12 months | 21% | 6% |
Concurrent CT-RT | Carboplatin–etoposide | 14 months | 25% | 8% |
Meta-Analysis 2010 | ||||
Sequential | Cisplatin + vinca or etoposide | 14 months | 30% | 11% |
Concurrent | 18 months | 36% | 15% | |
RTOG 0617 standard arm | Carboplatin–paclitaxel | 29 months | 58% | 31% |
PROCLAIM standard arm | Cisplatin–etoposide | 25 months | 52% | NA |
PACIFIC | CT-RT followed by Durvalumab | 47.5 months | 66% | 43% |
Variable | n (%) | Variable | n (%) |
---|---|---|---|
Overall population | 301 (100) | ||
Sex | Histology at diagnosis | ||
Female | 102 (33.9) | Adenocarcinoma | 198 (65.8) |
Male | 199 (66.1) | Squamous cell carcinoma | 85 (28.2) |
Median age at diagnosis | Adenosquamous cell carcinoma | 2 (0.7) | |
years (IQR) | 67 (61–72) | Sarcomatoid carcinoma | 2 (0.7) |
ECOG at diagnosis | Not otherwise specified | 14 (4.6) | |
0 | 133 (44.2) | PD-L1 % | |
1 | 162 (53.8) | <1% | 60 (19.9) |
>=2 | 6 (2) | ≥1% | 74 (24.6) |
Smoking habit | Unknown | 167 (55.5) | |
Never-smoker | 47 (15.6) | Driver mutation (EGFR, ALK, ROS1) | |
Former-smoker | 129 (42.9) | Positive | 24 (8) |
Current-smoker | 125 (41.5) | Negative or unknown | 277 (92) |
Chronic obstructive pulmonary disease | Stage at diagnosis | ||
No | 189 (62.8) | IIIA | 170 (56.5) |
Yes | 112 (37.2) | IIIB | 119 (39.5) |
Weight Loss | IIIC | 12 (4) | |
No | 256 (85) | Clinical T stage | |
Yes | 45 (15) | TX | 4 (1.3) |
Diagnostic techniques | T1 | 39 (13) | |
Bronchoscopy | 152 (50.5) | T2 | 86 (28.6) |
Image-guided transthoracic biopsy | 92 (30.6) | T3 | 85 (28.2) |
Mediastinoscopy | 14 (4.6) | T4 | 87 (28.9) |
Surgery | 43 (14.3) | Clinical N stage | |
N0 | 21 (7) | ||
N1 | 38 (12.6) | ||
N2 | 213 (70.8) | ||
N3 | 29 (9.6) |
Variable | n (%) | Variable | n (%) |
---|---|---|---|
Overall population | 301 (100) | ||
Therapeutic pathway | Adjuvant systemic therapy | 85 (28.2) | |
Surgery alone | 15 (5) | Platinum-based doublet | 78 (91.8) |
Neoadjuvant therapy → surgery +/− adjuvant radiotherapy | 119 (39.5) | Platinum-based doublet +/− immunotherapy | 5 (5.9) |
Surgery → adjuvant therapy | 89 (29.6) | Immunotherapy | 2 (2.3) |
Definitive chemo-radiation therapy (CT-RT) | 47 (15.6) | Adjuvant radiotherapy | 101 (33.6) |
Definitive CT-RT → durvalumab | 31 (10.3) | Adjuvant radiotherapy dose, Gy (range) | 54 (6–66) |
Therapeutic pathway: resectable vs unresectable | Definitive CT-RT +/− durvalumab | 78 (25.9) | |
Multimodality treatment with surgery | 223 (74.1) | Platinum-based doublet | 78 (100) |
Multimodality treatment without surgery | 78 (25.9) | Durvalumab | 31 (39.7) |
Neoadjuvant systemic therapy | 122 (40.5) | Radiotherapy | |
Platinum-based doublet | 115 (94.3) | Sequential | 33 (42.3) |
Platinum-based doublet +/− immunotherapy | 5 (4.1) | Concurrent | 45 (57.7) |
Immunotherapy | 1 (0.8) | Definitive radiotherapy dose, Gy (range) | 60 (12–66) |
Tyrosine kinase inhibitor | 1 (0.8) | ||
Neoadjuvant radiotherapy | 8 (2.7) | ||
Neoadjuvant radiotherapy dose, Gy (range) | 52.2 (50–60) |
Treatment Modality | Entire Population | ||
---|---|---|---|
No. of Patients (n = 301) | mRFS (Months) 95% CI | mOS (Months) 95% CI | |
Surgery alone | 15 | 16.4 (2.57 to 30.22) | 39.8 (27.88 to 51.82) |
Neoadjuvant therapy + surgery | 119 | 15.9 (11.27 to 20.53) | 41.5 (32.67 to 50.38) |
Surgery + Adjuvant therapy | 89 | 30.5 (20.42 to 40.58) | 64.1 (48.78 to 79.35) |
Chemo-radiation therapy | 47 | 11.4 (7.91 to 14.89) | 21.6 (7.89 to 35.28) |
Chemo-radiation therapy + durvalumab | 31 | 24.8 (12.12 to 37.48) | NR (NR to NR) |
Treatment Modality | Patients Treated After 2018 | ||
---|---|---|---|
No. of Patients (n = 161) | mRFS (Months) 95% CI | mOS (Months) 95% CI | |
Surgery alone | 11 | 16.4 (NR to 35.58) | 39.9 (25.96 to 53.74) |
Neoadjuvant therapy + surgery | 53 | 18 (13.27 to 22.73) | NR (NR to NR) |
Surgery + Adjuvant therapy | 39 | 23.9 (22.54 to 25.26) | 49.05 (24.71 to 73.39) |
Chemo-radiation therapy | 27 | 8.3 (4.93 to 11.68) | 17.4 (8.54 to 26.29) |
Chemo-radiation therapy + durvalumab | 31 | 24.8 (12.12 to 37.48) | NR (NR to NR) |
Treatment Modality | Unresectable Patients | ||
---|---|---|---|
No. of Patients (n = 78) | mRFS (Months) 95% CI | mOS (Months) 95% CI | |
Chemo-radiation therapy | 47 | 11.4 (7.91 to 14.89) | 21.6 (7.89 to 35.28) |
Chemo-radiation therapy + durvalumab | 31 | 24.8 (12.11 to 37.48) | NR (NR to NR) |
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Ferro, A.; Sepulcri, M.; Schiavon, M.; Scagliori, E.; Mancin, E.; Lunardi, F.; Gennaro, G.; Frega, S.; Dal Maso, A.; Bonanno, L.; et al. The Multidisciplinary Approach in Stage III Non-Small Cell Lung Cancer over Ten Years: From Radiation Therapy Optimisation to Innovative Systemic Treatments. Cancers 2022, 14, 5700. https://doi.org/10.3390/cancers14225700
Ferro A, Sepulcri M, Schiavon M, Scagliori E, Mancin E, Lunardi F, Gennaro G, Frega S, Dal Maso A, Bonanno L, et al. The Multidisciplinary Approach in Stage III Non-Small Cell Lung Cancer over Ten Years: From Radiation Therapy Optimisation to Innovative Systemic Treatments. Cancers. 2022; 14(22):5700. https://doi.org/10.3390/cancers14225700
Chicago/Turabian StyleFerro, Alessandra, Matteo Sepulcri, Marco Schiavon, Elena Scagliori, Edoardo Mancin, Francesca Lunardi, Gisella Gennaro, Stefano Frega, Alessandro Dal Maso, Laura Bonanno, and et al. 2022. "The Multidisciplinary Approach in Stage III Non-Small Cell Lung Cancer over Ten Years: From Radiation Therapy Optimisation to Innovative Systemic Treatments" Cancers 14, no. 22: 5700. https://doi.org/10.3390/cancers14225700