Guidelines
Copyright ©The Author(s) 2022.
World J Clin Oncol. Apr 24, 2022; 13(4): 237-266
Published online Apr 24, 2022. doi: 10.5306/wjco.v13.i4.237
Table 1 Level of evidence and grades of recommendation
Level of evidence
IEvidence from at least one large randomised controlled trial of good methodological quality (low potential for bias) or meta-analyses of well-conducted randomised trials without heterogeneity
IISmall randomised trials or large randomised trials with a suspicion of bias (lower methodological quality) or meta-analyses of such trials or of trials with demonstrated heterogeneity
IIIProspective cohort studies
IVRetrospective cohort studies or case-control studies
VStudies without control groups; case reports; expert opinions
Grades of recommendation
AStrong evidence for efficacy with a substantial clinical benefit, strongly recommended
BStrong or moderate evidence for efficacy but with a limited clinical benefit, generally recommended
CInsufficient evidence for efficacy or benefit does not outweigh the risk or the disadvantages (adverse events, costs, etc.), optional
DModerate evidence against efficacy or for adverse outcomes, generally not recommended
EStrong evidence against efficacy or for adverse outcome, never recommended
Table 2 Recommended stereotactic body radiation therapy dose in early-stage disease
Localization
Dose
Ref.
Evidence level
Central tumour50/5 fx-60/5 fxBezjak et al[43], 2019II, B
60 Gy/8 fxHaasbeek et al[46], 2011
Chest wall48 Gy/4 fxGuckenberger et al[47], 2017II, B
60 Gy/5 fxNagata et al[48], 2015
45 Gy/3 fxNyman et al[49], 2006
Safe zone30 Gy/1 fxSingh et al[50], 2019II, B
34 Gy/1 fxVidetic et al[31], 2019
54 Gy/3 fxTimmerman et al[36], 2018
Table 3 Accelerated fractionation-hyperfractionation studies
Ref.
Study type
Number of patients
Radiotherapy
Chemotherapy
Results
Toxicity
[65,66]Phase III RCTn = 563: Stage I (29%), II (7%), IIIA (38%), IIIB (23%). Similar in both arms[cRT: 60 Gy, 2 Gy/d (6 wk). INP 44 Gy + boost 16 Gy tumour and involved nodes] vs (CHART: 54 Gy, 1.5 Gy/3 times/d, 6 h apart, on 12 consecutive days). INP 37.5 Gy in 25 fx + boost 16.5 Gy in 11 Gy to tumour and involved nodesNoAbsolute 2-yr survival improvement of 9%: 20% cRT vs 29% CHART. 21% relative risk reduction for PL. Major improvement in squamous cell disease: 13% 2-yr survival: 20% cRT vs 33% CHART. 25% relative risk reduction of PLClinical pneumonitis 19% cRT and 10% CHART
[67]Phase III RCTn = 141: Stage III A-B unresectable. ECOG 0-1[cRT: 64 Gy, 2 Gy/d (6 ½ wk)] vs [HART: 57.6 Gy, 1.5 Gy 2 times/d (2.5 wk)]Induction: Carboplatin AUC 6 + paclitaxel 225 mg/m2 2 cycles prior to RT2-yr OS: 44% HART vs 24% cRT; 3 yr: 34% vs 14%. Non-significant trend towards better survival with HART. Feasible treatment. Trial close early due to slow recruitmentEsophagitis ≥ G3: 23% HART vs 15% cRT. Pneumonitis ≥ G3: 0 HART vs 10% cRT
[68]Phase III RCTn = 406: Stage I 10%, II 5%, IIIA 38%, IIIB 46%. Similar in both arms(CHARTWEL: 60 Gy, 1.5 Gy 2 times/d in 2.5 wk) vs (cRT: 66 Gy, 2 Gy/d, 6.5 wk)Neoadjuvant 27%. Similar in both armsBetter LC in CHARTWEL. No difference between arms in OS at 2, 3, 5 yr. Better LC CHARTWEL trend in advanced stages and after neoadjuvant ChTGreater acute dysphagia CHARTWEL. Greater radiological pneumonitis CHARTWEL, no differences in clinical pneumonitis
[69]Retrospectiven = 849, 9 United Kingdom centres. Stage I 33%, II 13%, IIIA 24%, IIIB 24%, IV 1%CHART: 54 Gy, 1.5 Gy/3 times/d, 6 h apart, in 12 dInduction: 27% patients, 82% stage III (96% platinum doublets: Cisplatin or carboplatin with vinorelbine, gemcitabine or paclitaxel)OS 2 and 3 yr: 47% and 32%. OS 3 yr: 38% stage I and 27% stage III. Tendency to better survival in stage III after ChTEsophagitis, pneumonitis ≥ G3 5%
Table 4 Studies of moderate hypofractionated radiotherapy
Ref.
Type of study
Number of patients
Radiotherapy
Chemotherapy
Results
Toxicity
[76]Prospective30, stage III-IVA. ECOG ≥ 260 Gy (20 fx 3 Gy); (BED10 79.4 Gy)Sequential (80% patients)LR 37%. OS 2-yr 38.1%. LR 37%. Distant relapse 57%Acute esophagitis G3 7%. Acute pneumonitis G3 3%. No chronic toxicity
[77]Prospective83 (32 stage III)66 Gy (24 fx 2.75 Gy); (BED10 84 Gy)Sequential 90.6% stage III (platinum + vinorelbine)OS 2 yr 37.5%. SCE 2 yr 41.5%No toxicity ≥ G3
[78]Retrospective300, stage III, inoperable, MEG3 arms: 45 Gy (15 fx 3 Gy); 60-63 Gy (6 wk); > 63 Gy (6 wk)No significant differences in LC, distant control, or OS. > DFS in 60-63 GyLower in hypofractionated arm
[79]Retrospective 609 (9 centres). Stage IA (18%), IB (30.7%), II (14.8%), IIIA (16.4%), IIIB (19.2%). Unresectable or inoperable55 Gy (20 fx 2.75 Gy)ChT 28% (83% stage III). Platinum doublets. Most neoadjuvantOS at 2, 3 and 5 yr: 50%, 36% and 20%. 2 yr OS: stage IA, 72%, stage Ib 51%, stage IIIA 40%. Adenocarcinoma better median survival (31 m) vs squamous (20.4 m). No difference in OS between ChT vs no ChT. Stage III, trend towards better OS with ChTNo toxicity ≥ G3. Pneumonitis G1-2, 15%
[80,82]Retrospective31, stage I (15), II (15), IIIA (57), IIIB (43). Medically inoperable or unresectable3 arms: 66 Gy (24 fx 2.75 Gy) + daily cisplatin (6 mg/m2); same sequential RT after 2 cycles cisplatin/gemcitabine; RT alone 66 Gy (24 fx 2.75 Gy) or 60 Gy (20 fx 3 Gy)Concurrent: Cisplatin daily (6 mg/m2). Sequential: (2 cycles cisplatin/gemcitabine) prior to RTLR 36%, DM 46%. Better RT + ChT than RT alone. 5 yr OS: Concurrent CRT, 23%. No significant difference between concurrent and sequential CRT. LR 36%, DM 46%Severe late toxicity greater in CRT (27% concurrent, 23% sequential) than in RT alone (8%)
[81]Phase III RCT160, stage II/III (11.6%/88.3%). ECOG ≥ 2. Not candidates for ChT/RTcRT 60-66 Gy/30-33 fx vs accelerated hypofx 60 Gy/15 fx 4 GyNon-concurrent ChT. Possible neoadjuvant or adjuvantOS and PFS without significant differences between cRT and hypofxNo G4 toxicity. G3 toxicity: 35% cRT and 18.75% hypofx
[82]Phase III RCT158, stage I (3% sequential, 1% concurrent), II (4% sequential, 5% concurrent), IIIA (45% sequential, 30% concurrent), IIIB (47% sequential, 64% concurrent). Inoperable ECOG 0-166 Gy (24 fx 2.75 Gy)Concurrent: Daily cisplatin (6 mg/m2) + RT 66 Gy (24 fx 2.75 Gy) vs sequential: 2 cycles gemcitabine 1250 mg/m2 days 1, 8 and cisplatin (75 mg/m2 day 2, prior to RT 66 Gy (24 fx 2.75 Gy)No significant differences between the 2 groups in DM, OS, PFS. OS 2 and 3 yr: 39%-34% concurrent and 34%-22% sequential. Both schemes well tolerated. Due to early closure, no conclusions drawnAcute esophagitis G3/4 more common in concurrent (14% vs 5%). Late esophagitis G3 = 4% in both arms. Pneumonitis G3/4 = 18% concurrent and 14% sequential
[83]Phase II RCT130, stage III inoperable. ECOG 0-155 Gy (20 fx 2.75 Gy)Concurrent: Cisplatin 20 mg/m2 days 1-4 and 16-19 and vinorelbine 15 mg/m2 days 1, 6, 15 and 20 RT and 1 or 2 post ChT cycles (CDDP) 80 mg/m2 day 1 and vinorelbine 25 mg/m2 days 1 and 8). Sequential: Cisplatin 80 mg/m2 day 1 and vinorelbine 25 mg/m2 days 1 and 8, x 3-4 cycles before RTNo significant differences. OS 1 yr: 70% concurrent vs 83% sequential and 2 yr: 50% concurrent vs 46% sequential. PFS 1 yr: 74% concurrent vs 85% sequential; 2 yr: 47% concurrent vs 45% sequential. Both safe and effective treatments. Non-significant trend towards better survival with concurrent RT/ChTSimilar esophagitis ≥ G3 in both arms (8.8% concurrent and 8.5% sequential. Pneumonitis ≥ G3: 3.1% concurrent vs 5.2% sequential. No grade 4/5 esophagitis. G3 neutropenia lower in concurrent (37%) vs sequential (55%)
[84]Retrospective100, stages IIIA-B 95%, II 5%. ECOG 0/155 Gy (20 fx 2.75 Gy)Concurrent: Cisplatin 20 mg/m2 days 1-4 and 16-19 RT and vinorelbine 15 mg/m2 days 1, 6, 15, 20 and 2 cycles post RT/ChTOS 2 yr 58%. PFS 2 yr 49%Esophagitis G3/4 14%. Pneumonitis G3/4 4%
Table 5 Radiation therapy in patients with oligometastatic non-small cell lung cancer
Ref.
Type
Design
Palliative treatment
Histology
Presentation
No. of metastases/location
RT type
Follow-up (mo)
PFS (mo)
MFS (mo)
OS (mo)
Gomez et al[93], 2019Phase II RCT. MulticentreInduct. ChT: (RT + MT) vs MT49NSCLC (No EGFR, ALK)Synchronous. Metachronous≤ 3 (1%:65%)/lung, CNS, bone, liver SSRR, nodesSABR/SBRT (MTX) hypofra. RT (primary)38.814.2 (SABR/SBRT + MT) vs 4.4 (MT)11.9 (SABR/SBRT + MT) vs 5.741 (SABR/SBRT + MT) vs 17
Iyengar et al[95], 2018Phase II RCT. MulticentreInduct. ChT: (SBRT + mChT) vs mChT29NSCLC (No GFR, ALK)Synchronous≤ 5 (1%:21%, 2%-3%:76%)/lung, lymph, bone, SSRRSABR/SBRT (MTX) hypofra. RT (primary)9.619.7 (SABR/SBRT + MT) vs 3.5 (MT)NRNR (SABR/SBRT + MT) vs 17
Palma et al[94], 2020Phase II RCT. Multicentre(ChT + PT) vs (ChT + SABR/SBRT)99Lung (18/99)Synchronous. Metachronous≤ 5 (1%-3%:93%)/lung, bone, CNS, liver, SSRRSABR/SBRT5111.6 (SABR/SBRT + MT) vs 5.4 (TP-MT)NR50 (SABR/SBRT + MT) vs 22
Table 6 Prognostic factors associated with better survival in oligometastatic patients with non-small cell lung cancer
Factor
Comments
GenderFemale > male
HistologyAdenocarcinoma > squamous cell carcinoma
PresentationMetachronous > synchronous
Karnofsky index - ECOG80% < - ≤ 100%
Number of lesions1 > 2-3 > 4-10
Size< 3 cm
LocationLung, bone > adrenal glands, lymph nodes > liver, brain
Table 7 Dose constraints in normofractionated radiotherapy
Organ
Volume
Endpoint
Dose (Gy), dose/volume
Rate, %
Ref.
Spinal cordPartialMyelopathyDmax 50, Dmax 60, Dmax 690.2%, 6%, 50%
LungWhole organ, both lungsPneumonitisV20 ≤ 30%, MD = 7, MD = 13, MD = 20, MD = 24, MD = 27< 20%, 5%, 10%, 20%, 30%, 40%Palma et al[133], 2013 Marks et al[130], 2010
EsophagusWhole organ≥ Grade 3 acute esophagitis, ≥ grade 2 acute esophagitisMD < 34, V60 ≤ 17%, V35 < 50%, V50 < 40%, V70 < 20%5%-20%, < 30%, < 30%, < 30%Al-Halabi et al[135], 2015
HeartPericardium. Whole organ Pericarditis. Cardiac mortality long termMD < 26, V30 < 46%, V25 < 10%, V50 ≤ 25%< 15%, < 15%, < 1%Speirs et al[136], 2017
Brachial plexusWhole organBrachial plexopathyMD > 69 Gy. Dosis maximum 75 Gy to 2 cc of the brachial plexusAmini et al[137], 2012
Table 8 Dose constraints for moderate hypofractionation
Organ
Concurrent RT/ChT (55 Gy/20 fx)
Sequential RT/ChT (55 Gy/20 fx)
RT (50-58 Gy/15 fx)
RT (50-60 Gy/15 fx)[138]
Spinal cordMD 44 Gy (0.1 cc)Dmax ≤ 36MD 42 Gy (0.1 cc)MD < 38 Gy
Esophagus1MD < 55 Gy (1 cc)V42 < 32%MD < 52 Gy (1 cc)MD < 50 Gy (1 cc), V45 < 10 cc
Lungs-GTVV20 < 35%, MD < 18 GyV20 < 25%-30%, MD ≤ 15 GyV19 < 35%, MD < 16 GyV20 < 30%, V5 < 60%, MD < 20 Gy
HeartV30 < 36%V33 < 25%D100% < 33 Gy, D67% < 40 Gy, D33% < 52 GyMD 63 Gy, V57 < 10 cc
Great vesselsNANAMD 58 GyMD 63 Gy, V57 < 10 cc
Trachea, carina and main bronchusNANAMD 58 GyMD 63 Gy, V57 < 10cc
RibMD < 63 GyNAV30 < 30 ccMD 63 Gy; V30 < 30cc
Table 9 The constraints to organs at risk s in stereotactic body radiotherapy based on the studies
Organ
Single fraction (30-34 Gy)
Three fractions (54-60 Gy)
Four fractions (48 Gy)
Five fractions (50-60 Gy)
Eight fractions (60 Gy)
Ref.
Optimal
Mandatory
Optimal
Mandatory
Optimal
Mandatory
Optimal
Mandatory
Optimal
Mandatory
Brachial plexus14 Gy < 3 cc17.5 Gy ≤ 0.035 cc20.4 Gy < 3cc24 Gy ≤ 0.035 cc27 Gy < 3 cc30.5 Gy ≤ 0.035 ccBenedict et al[139], Grimm et al[140]
14.4 Gy < 3cc17.5 Gy Dmax22.5 Gy < 3 cc24 Gy30 Gy < 3 cc32 GyBezjak et al[43]
23.6 Gy < 3 cc, 30 Gy < 10 cc, 35 Gy < 1 cc27.2 Gy Dmax, 40 Gy DmaxVidetic et al[31], Chang et al[146]
24 Gy ≤ 0.5 cc26 Gy ≤ 0.5 cc27 Gy ≤ 0.5 cc29 Gy ≤ 0.5 cc27 Gy ≤ 0.5 cc38 Gy ≤ 0.5 ccHanna et al[141]
Spinal cord10 Gy < 0.35 cc, 7 Gy < 1.2 cc14 Gy ≤ 0.035 cc14 Gy < 0.35 cc, 12.3 Gy < 1.2 cc18 Gy ≤ 0.035 cc23 Gy < 0.35 cc, 14.5 Gy < 1.2 cc30 Gy ≤ 0.035 ccBenedict et al[139]
7 Gy < 1.2 cc7 Gy < 1.2 cc18 Gy < 0.25 cc, 11.1 Gy < 1.2 cc18 Gy20.8 Gy < 0.35 cc, 13.6 Gy < 1.2 cc26 Gy Dmax22.5 Gy < 0.25 cc, 13.5 Gy < 1.2 cc, 13.5 Gy < 0.5 ccBezjak et al[43], Videtic et al[31], Timmerman et al[36]
18 Gy < 0.1 cc21.9 Gy < 0.1 cc23 Gy < 0.1 cc30 Gy < 0.1 cc25 Gy < 0.1 cc32 Gy < 0.1 ccHanna et al[141]
Esophagus11.9 Gy < 5 cc, 14.5 Gy < 5 cc15.4 Gy Dmax17.7 Gy < 5 cc25.2 Gy19.5 Gy < 5 cc35 GyVidetic et al[31]
21 Gy < 5 cc27 Gy18.8 Gy < 5 cc, 30 Gy < 10 cc, 35 Gy < 1 cc30 Gy Dmax, 50 Gy Dmax27.5 Gy < 5 cc35 Gy, 52.5 GyTimmerman et al[36], Bezjak et al[43], Chang et al[146]
25.2 Gy < 0.5 cc32 Gy < 0.5 cc34 Gy < 0.5 cc40 Gy < 0.5 ccHanna et al[141]
Heart16 Gy < 15 cc, 16 Gy < 15 cc22 Gy Dmax, 22 Gy Dmax24 Gy < 15 cc, 24 Gy < 15 cc30 Gy Dmax, 30 Gy Dmax28 Gy < 15 cc, 35 Gy < 10 cc, 40 Gy < 1 cc34 Gy Dmax, 50 Gy Dmax32 Gy < 15 cc, 32 Gy < 15 cc38 Gy Dmax, 38 Gy Dmax, 52.5 Gy DmaxBenedict et al[139], Timmerman et al[36], Bezjak et al[43], Chang et al[146]
24 Gy < 0.5 cc26 Gy < 0.5 cc27 Gy < 0.5 cc29 Gy < 0.5 cc50 Gy < 0.5 cc60 GyHanna et al[141]
Great Vessels31 Gy < 10 cc37 Gy Dmax39 Gy < 10 cc45 Gy Dmax47 Gy < 10 cc53 Gy DmaxBenedict et al[139]
31 Gy < 10 cc37 Gy < 0.035 cc39 Gy < 10 cc45 Gy Dmax43 Gy < 10 cc, 35 Gy < 10 cc, 40 Gy < 1 cc49 Gy Dmax47 Gy < 10 cc52.5 Gy DmaxBezjak et al[43], Videtic et al[31], Chang et al[146]
45 Gy < 0.5 cc53 Gy < 5 ccHanna et al[141]
Trachea and bronchus10.5 Gy < 4 cc20.2 Gy Dmax15 Gy < 4 cc30 Gy Dmax16.5 Gy < 4 cc40 Gy DmaxBenedict et al[139]
8.8 Gy < 4 cc, 10.5 Gy < 4 cc22 Gy Dmax, 20.2 Gy < 0.035 cc21 Gy < 5 cc30 Gy Dmax30 Gy < 10 cc, 35 Gy < 1 cc, 15.6 Gy < 4 cc50 Gy Dmax, 34.8 Gy DmaxBezjak et al[43], Videtic et al[31], Timmerman et al[36], Chang et al[146]
30 Gy < 0.5 cc32 Gy < 0.5 cc32 Gy < 0.5 cc35 Gy < 0.5 cc32 Gy < 0.5 cc44 Gy < 0.5 ccHanna et al[141]
Skin23 Gy < 10 cc, 14.4 Gy < 10 cc26 Gy Dmax, 16 Gy Dmax30 Gy < 10 cc, 22.5 Gy < 10 cc33 Gy Dmax, 24 Gy Dmax35 Gy < 10 cc, 40 Gy < 1 cc, 33.2 Gy < 10 cc36 Gy Dmax36.5 Gy < 10 cc, 30 Gy < 10 cc39.5 Gy Dmax, 32 Gy DmaxBenedict et al[139], Chang et al[146], Videtic et al[31]
Chest wall22 Gy < 1 cc30 Gy Dmax28.8 Gy < 1 cc, 30 Gy < 30 cc36.9 Gy Dmax35 Gy < 1 cc43 Gy DmaxBenedict et al[139]
22 Gy < 1 cc30 Gy Dmax30 Gy < 30 cc, 50 Gy < 2.3 cc35 Gy < 10 cc, 32 Gy < 1 cc40 Gy Dmax30 Gy < 30 cc, 50 Gy < 2.3 cc, 60 Gy < 1.4 ccVidetic et al[31], Kong et al[145], Liao et al[147]
37 Gy < 0.5 cc, 30 Gy < 30 cc39 Gy < 0.5 cc, 32 Gy < 30 cc39 Gy < 0.5 cc, 35 Gy < 30 ccHanna et al[141], Dunlap et al[142], Ma et al[143]
40 Gy < 5 cc, 60 Gy < 0.5 ccV30 < 30 cc, V30 < 70 ccHerth et al[19]
Normal lungsMinimal critical volume under threshold. 1500 cc, 1000 ccThreshold dose: 7 Gy, 7.4 GyThreshold dose: 11.6 Gy, 12.4 GyThreshold dose: 12.5 Gy, 13.5 GyBenedict et al[139]
Minimal critical volume under threshold. 1500 cc, 1000 cc, 1500 cc, 1000 cc7 Gy, 7.4 Gy20 Gy < 10%, 20 Gy < 15%10.5 Gy, 11.4 Gy11.6 Gy, 12.4 Gy, 20 Gy < 20%, 30 Gy < 10%12.5 Gy, 13.5 Gy, 20 Gy < 20%, 30 Gy < 10%Bezjak et al[43], Videtic et al[31], Chang et al[146]
V20 < 10%, V12.5 < 15%V20 < 10%, V12.5 < 15%V20 < 10%, V12.5 < 15%Hanna et al[141]
Treatment on lesion: V20 < 10%; treatment 2-3 lesions: V20 < 12.5% (optimal); V20 < 15% (acceptable); V20 < 20% (selected cases) 3-8 fractions on alternating days. If the lesions are not included in the treatment field, alternate the treatment days for the different lesionsHanna et al[141]
In 3-5 fraction Dmean ≤ 8 Gy and V20 ≤ 10%-15%Kong et al[145]
Table 10 Summary of recommendations
Diagnosis
Level of evidence, grade of recommendation
If lung cancer is suspected, refer patient to a rapid diagnostic service for evaluation by a multidisciplinary teamII, C
PET-CT is recommended for initial staging in patients with stage I-III disease who are candidates for radical treatmentI, A
EBUS/EUS is recommended for clinical staging in patients with enlarged lymph nodes without distant metastases, with or without PET uptakeI, C
EBUS/EUS is recommended for stating in patients with positive PET-CT scans and normal-sized lymph nodes without distant metastasesI, A
Histological confirmation of the mediastinum by EBUS/EUS is recommended in central tumours, tumours > 3 cm, and N1 casesI, C
Histological confirmation is required in cases with a single metastatic lesion and positive PET-CTII, A
Brain MRI is recommended in candidates for curative-intent treatment II, A
VAMS should be performed when EBUS/EUS findings are not evaluableI, B
Differentiation between adenocarcinomas and squamous cell carcinomas is recommended even for small biopsies or cytologyI, B
EGFR mutations and ALK rearrangements should be assessed in patients with stage IV, non-squamous cell carcinomas. This determination should be performed in all cases (regardless of smoking status) and in all non-smokers independently of tumour histologyI, B
Early stage NSCLC - SBRT
InoperableII, A
OperableIII, C
High surgical riskIII, A
Locally-advanced disease
Concomitant radiotherapy: This is the treatment of choice for unresectable stage IIIA/IIIB with ECOG 0-1 and weight loss < 5% in 3 moI, A
60-66 Gy in 30-33 daily fractions of 2 Gy/fx and 2-4 ChT cyclesI, A
Platinum-based ChTI, A
Treatment should be completed in < 7 wkIII, B
Sequential radiotherapy
If concomitant treatment is not possible, the alternative is sequential CRTI, A
Treatment should be completed in a short period of timeI, A
Neoadjuvant radiotherapy
Assessment by a multidisciplinary team is recommendedIV, C
In potentially-resectable upper sulcus tumours, the recommended approach is neoadjuvant CRT followed by surgeryIII, A
This approach can be considered in potentially-resectable T3/T4 tumours, but only in well-selected cases at experienced centresIII, B
Surgery must be performed within 4 wk after completion of RTIII, B
Adjuvant radiotherapy
Not recommended in early stage disease with complete resection (R0)I, A
It should be considered if resection is incomplete or margins are involved (R1)IV, B
Not recommended as standard in R0 cases with N2 involvement I, A
In N2 disease, adjuvant RT could be considered based on risk factors for local recurrenceIV, C
If adjuvant ChT and RT are both administered, the recommended sequence is ChT followed by RTV, C
Altered fractionation schemes
Accelerated hyperfractionation schemes provide better disease control than conventional RTI, A
Recommended fractionation schemes for RT administered alone or sequentially after ChT: 55 Gy (20 fx, 2.75 Gy), 60 Gy (20 fx, 3 Gy), 60 Gy (15 fx, 4 Gy), 45-50 Gy (15 fx, 3-3.33 Gy)II, A
If RT administered concurrently with ChT in patients with good performance status: 55 Gy (20 fx 2.75 Gy)II, B
General considerations: There is no evidence to support prophylactic WBRT in stage III diseaseII, A