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©The Author(s) 2021.
World J Clin Oncol. Mar 24, 2021; 12(3): 115-143
Published online Mar 24, 2021. doi: 10.5306/wjco.v12.i3.115
Published online Mar 24, 2021. doi: 10.5306/wjco.v12.i3.115
Table 1 Chronological changes in the combined treatment of small cell lung cancer
Chronological changes in SCLC treatment | |||||||
Ref. | Stage (LS or ES) | Phase | Treatment | Median survival | 5-yr survival | P value | Level of evidence |
Miller et al[4] 1969 | LS | III | RT | 28.5 wk; 43 wk | 1%; 5% | 0.04 | A I |
Bergsagel et al[8] 1972 | LS | III | RT; RT + Ch | 21 wk; 42 wk | NR | < 0.05 | A I |
Einhorn et al[13] 1976 | LS | II | RT + PCT | 12 mo | 10% | C III | |
Bunn et al[18] 1987 | LS | III | PCT; PCT + RT | 12 mo; 15 mo | 10%; 15% | < 0.05 | A I |
Turrisi et al[27] 1988 | LS | II | Early AHF-RT + CE | 23 mo | 30% at 3 yr | C III | |
Murray et al[26] 1993 | LS | III | Early RT + CE; late RT + CE | 21 mo; 19 mo | 20%; 13% | < 0.05 | A I |
Pignon et al[21] 1992 | LS | Meta-analysis | PCT (no CE); PCT (no CE) + TRT | < 14% mortality | > 5% at 3 yr | 0.001 | A I |
Jeremic et al[29] 1997 | LS | III | Early AHF-RT + CE; late AHF-RT + CE | 36 mo; 34 mo | 30%; 15% | 0.0027 | A I |
Turrisi et al[31] 1999 | LS | III | Early AHF-RT + CE; early NFRT + CE | 23 mo; 19 mo | 26%; 16% | 0.04 | A I |
Jeremic et al[41] 1999 | ES | III | PCT + RT + PCI; PCT + PCI | 17 mo; 11 mo | 9.1%; 3.7% | 0.0041 | A I |
Aupérin et al[33] 1999 | LS | Meta-analysis | PCI; no PCI | > 6% at 3 yr | A I | ||
Takada et al[30] 2002 | LS | III | Early AHF-RT + CE; late AHF-RT + CE | 31.3 mo; 20.8 mo | 24%; 18% | < 0.05 | A I |
Slotman et al[38] 2007 | ES | III | CE + PCI; CE | 27% at 1 yr; 13% at 1 yr | < 0.001 | A I | |
Slotman et al[42] 2015 | ES | III | CE + PCI; CE + TRT + PCI | 3% at 3 yr; 13% at 3 yr | < 0.03 | A I | |
Faivre-Finn et al[43] 2017 | LS | III | CE + AHF-RT 45 Gy; CE + NFRT 66 Gy | 29 mo; 19 mo | 34%; 31% | NS | A I |
Table 2 Diagnostic staging recommendations for small cell lung cancer
Diagnosis of small cell lung carcinoma |
Staging with combined VALSG and TNM AJCC 8th edition (I, A) |
Baseline study |
Age, tobacco use, comorbidities, complete physical examination, and ECOG PS |
Complete blood analysis: Blood count, biochemistry, liver and kidney function, alkaline phosphatase, LDH |
Cardiology study: Electrocardiogram +/- echocardiogram |
Respiratory function testing in patients expected to receive locoregional treatment |
CT with intravenous contrast (unless medically contraindicated) |
Upper thoracoabdominal CT with intravenous contrast; include pelvis in advanced stages |
Intravenous contrast improves the definition of central tumours and lymph node involvement (III, A) |
18F-FDG PET/CT |
18F-FDG PET/CT recommended in patients expected to undergo locoregional treatment (III, A) |
Images are acquired with the patient in the radiotherapy treatment position according to consensus protocol between Nuclear Medicine and Radiation Oncology departments (IV, A) |
Not recommended for restaging after chemotherapy in sequential treatment |
Brain staging |
Brain MRI is preferable |
Brain CT with IV contrast (without contrast is inadequate) |
Bone scintigraphy |
Only indicated if PET/CT is not available |
Abdominal MRI |
Only indicated to assess uncertain liver or adrenal lesions (V, C) |
Histological confirmation |
Invasive tests used as appropriate according to tumour location |
Follow WHO criteria for cell typing. Immunohistochemistry for differential diagnosis |
Table 3 Tumor-node-metastasis American Joint Committee on Cancer 8th edition lung cancer
TNM AJCC 8th edition lung cancer | |
T: Primary tumour | |
Tx | Not evaluable by imaging or malignant cells in sputum or bronchial lavage |
T0 | No evidence of primary tumour |
Tis | Carcinoma in situ |
T1 | ≤ 3 cm surrounded by lung or visceral pleura, or lobar bronchus |
T1a (mi) | Minimally invasive |
T1a | ≤ 1 cm |
T1b | > 1 cm to ≤ 2 cm |
T1c | > 2 cm to ≤ 3 cm |
T2 | > 3 cm to ≤ 5 cm, or involving main bronchus without affecting the carina, visceral pleura, or atelectasis or obstructive pneumonitis extending to the hilar region, affecting part or all of the lung |
T2a | > 3 cm to ≤ 4 cm |
T2b | > 4 cm to ≤ 5 cm |
T3 | > 5 cm to ≤ 7 cm, or tumour nodules in the same lobe, or invasion of the chest wall (parietal pleura), phrenic nerve, parietal pericardium |
T4 | > 7 cm, or nodules in a different ipsilateral lobe or invasion of the diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, and carina |
N: Regional lymph node involvement | |
Nx | Not evaluable |
N0 | No node involvement |
N1 | Ipsilateral peribronchial and/or hilar and intrapulmonary nodes |
N2 | Ipsilateral mediastinal nodes and/or subcarinal |
N3 | Contralateral mediastinal or contralateral hilar nodes, or any scalene or supraclavicular nodes |
M: Distant metastasis | |
M0 | No metastasis |
M1 | Distant metastasis |
M1a | Nodules in contralateral lobe; pleural or pericardial or pleural or pericardial effusion |
M1b | Single extrathoracic metastasis (including non-regional lymph node) |
M1c | Multiple extrathoracic metastases |
Table 4 Grouping by tumor-node-metastasis stage: American Joint Committee on Cancer 8th edition lung cancer
TNM AJCC 8th edition lung cancer grouping by stage | |||
Occult carcinoma | Tx | N0 | M0 |
Stage 0 | Tis | N0 | M0 |
Stage IA1 | T1a (mi)-T1a | N0 | M0 |
Stage IA2 | T1b | N0 | M0 |
Stage IA3 | T1c | N0 | M0 |
Stage IB | T2a | N0 | M0 |
Stage IIA | T2b | N0 | M0 |
Stage IIB | T1-2 | N1 | M0 |
T3 | N0 | M0 | |
Stage IIIA | T1-2 | N2 | M0 |
T3 | N1 | M0 | |
T4 | N0-1 | M0 | |
Stage IIIB | T1-2 | N3 | M0 |
T3-4 | N2 | M0 | |
Stage IIIC | T3-4 | N3 | M0 |
Stage IVA | Any T | Any N | M1a-b |
Stage IVB | Any T | Any N | M1c |
Table 5 Planning volumes in the principal studies of concurrent chemoradiotherapy in small cell lung cancer
Ref. | Study | Volume |
Jeremic et al[41] 1999 | Prospective, randomised | GTV + hilum + 2 cm; entire mediastinum + both supraclavicular fossae + 1 cm |
Zhu et al[116] 2011 | Retrospective | Primary GTV + GTVn > 1 cm short axis |
Yee et al[117] 2012 | Prospective, phase II | GTVp + GTVn visible on planning CT |
Slotman et al[44] 2015 | Phase III, randomised | GTVp post-CT + 15 mm + ipsilateral hilum + nodes involved pre-CT |
Luan et al[119] 2015 | Retrospective | CR post-CT: Primary GTV bed and GTVn involved pre-CT; SD post-CT: GTVp + GTVn; PD post-CT: New GTVp + GTVn + GTV |
Qin et al[118] 2016 | Retrospective | GTV: Thoracic, mediastinal, and supraclavicular fossae |
Gore et al[47] 2017 | Phase II, randomised | Post-CT volume including the primary tumour and nodal areas involved at diagnosis |
Luo et al[120] 2017 | Retrospective | Post-CT GTVp + pre-CT primary tumour bed + GTVn of nodes involved pre-CT |
Zhang et al[121] 2017 | Literature review | CR: Mediastinum initially involved; PR: Residual pulmonary lesions + initially involved lymph nodes |
Table 6 Summary of the main studies of prophylactic cranial irradiation in small cell lung cancer
PCI in SCLC | ||||||||
Ref. | Stage (LS or ES) | Phase | Treatment | Survival | P value | Incidence of BM | P value | Level of evidence |
Arriagada et al[144] 2002 | LS | III | PCI; no PCI | 18% at 5 yr; 15% at 5 yr | 0.06 | 20% at 5 yr; 37% at 5 yr | < 0.001 | A I |
Aupérin et al[33] 1999 | LS | Meta-analysis | PCI; no PCI | 20.7%; 15.3% | 0.01 | 0.38; 0.57 | 0.001 | A I |
Warde et al[20] 1992 | LS | Meta-analysis | PCI; no PCI | HR 0.82 | HR 0.48 | A I | ||
Takahashi et al[122] 2017 | ES | III | PCI; MRI + no PCI | 13.6 mo; 11.6 mo | 48%; 69% | A I | ||
Rusthoven et al[81] 2020 | III | WBRT; SRS | 5.2 mo; 6.5 mo | 0.003 | A I | |||
Yin et al[145] 2019 | Meta-analysis | PCI; observation | HR 0.81 | < 0.001 | HR 0.45 | < 0.001 | A II | |
De Ruysscher et al[146] 2018 | III | PCI; observation | 24.2 mo; 21.9 mo | 0.56 | 7%; 27.2% | 0.001 | A I | |
Slotman et al[38] 2007 | ES | III | PCI; no PCI | 6.7 mo; 5.4 mo | 15% at 1 yr; 40% at 1 yr | < 0.001 | A I | |
Le Péchoux et al[154] 2009 | LS | III | Standard dose PCI; high dose PCI | 42%; 37% | 0.05 | 29% at 2 yr; 23% at 2 yr | 0.18 | A I |
Ref. | Stage (LS or ES) | Phase | Treatment | Median Survival | P value | Incidence of neurological deficit | P value | Level of evidence |
Yang et al[157] 2018 | LS | Meta-analysis | PCI; no PCI | HR 0.52 | RR 0.5 | A I | ||
Viani et al[148] 2012 | LS-ES | Meta-analysis | PCI; no PCI | OR 0.73 | 0.01 | |||
Ge et al[149] 2018 | ES | Meta-analysis | PCI; no PCI | HR 0.57 | < 0.001 | RR 0.47 | < 0.01 | A I |
Brown et al[164] 2020 | III | HA + WBRT + Memantine; WBRT + Memantine | Learning 11.5%, memory 16.4%; learning 24.7%, memory 33.3% | 0.049; 0.02 | AI | |||
van Meerbeeck et al[165] 2019 | III | PCI; PCI + HA | HVLT-R 28%; 29% | > 0.05 | A I | |||
De Dios et al[167] 2019 | LS-ES | III | PCI; PCI + HA | FCSRT 21.7%, 32.6%, and 18.5% at 3, 6 and 12 mo; FCSRT 5.1%, 7.3% and 3.8% at 3, 6 and 12 mo | < 0.05 | AI |
- Citation: Couñago F, de la Pinta C, Gonzalo S, Fernández C, Almendros P, Calvo P, Taboada B, Gómez-Caamaño A, Guerra JLL, Chust M, González Ferreira JA, Álvarez González A, Casas F. GOECP/SEOR radiotherapy guidelines for small-cell lung cancer. World J Clin Oncol 2021; 12(3): 115-143
- URL: https://www.wjgnet.com/2218-4333/full/v12/i3/115.htm
- DOI: https://dx.doi.org/10.5306/wjco.v12.i3.115