Abstract

Objective

The present study was performed to assess the usefulness of involved-field irradiation and the impact of 18F-fluorodeoxyglucose-positron emission tomography-based staging on treatment outcomes in limited-stage small cell lung cancer.

Methods

Eighty patients who received definitive chemoradiotherapy for limited-stage small cell lung cancer were retrospectively analyzed. Fifty patients were treated with involved-field irradiation, which means that the radiotherapy portal includes only clinically identifiable tumors. The other 30 patients were irradiated with a comprehensive portal, including uninvolved mediastinal and/or supraclavicular lymph nodes, so-called elective nodal irradiation. No significant difference was seen in clinical factors between the two groups.

Results

At a median follow-up of 27 months (range, 5–75 months), no significant differences were observed in 3 year overall survival (44.6 vs. 54.1%, P= 0.220) and 3 year progression-free survival (24.4 vs. 42.8%, P= 0.133) between the involved-field irradiation group and the elective nodal irradiation group, respectively. For patients who did not undergo positron emission tomography scans, 3 year overall survival (29.3 vs. 56.3%, P= 0.022) and 3 year progression-free survival (11.0 vs. 50.0%, P= 0.040) were significantly longer in the elective nodal irradiation group. Crude incidences of isolated nodal failure were 6.0% in the involved-field irradiation group and 0% in the elective nodal irradiation group, respectively. All isolated nodal failures were developed in patients who had not undergone positron emission tomography scans in their initial work-ups.

Conclusion

If patients did not undergo positron emission tomography-based staging, the omission of elective nodal irradiation resulted in impaired survival outcomes and raised the risk of isolated nodal failure. Therefore, involved-field irradiation for limited-stage small cell lung cancer might be reasonable only with positron emission tomography scan implementation.

INTRODUCTION

Several meta-analyses and randomized trials have demonstrated survival benefits of concurrent chemoradiotherapy for limited-stage small cell lung cancer (LS-SCLC) (1–6). One of the controversies among radiation oncologists is how to treat regional lymph nodes (LNs). Historically, radiotherapy (RT) portal included all mediastinal LNs and/or supraclavicular LNs irrespective of initial disease extent (1,4,5,7–9). Omission of elective nodal irradiation (ENI) is becoming increasingly prevalent among modern studies (10–12), however, no uniform consensus has been reached on the most appropriate extent of nodal irradiation in the field of SCLC.

Recent prospective and retrospective studies reported a low risk of isolated nodal failure (INF) without ENI, especially when 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) was performed as the initial staging work-up; these studies also supported the practice of involved-field irradiation (IFI) (13–15).

The present study evaluates the usefulness of IFI in LS-SCLC patients treated with definitive chemoradiotherapy and the impact of PET-based staging on treatment outcomes.

PATIENTS AND METHODS

Patient Characteristics

Between July 2004 and July 2009, 84 patients with LS-SCLC received definitive thoracic RT (TRT) and chemotherapy. Excluding 4 patients to whom inadequate radiation doses (range, 4–24 Gy) were delivered due to non-treatment related morbidity or patient's non-compliance, we analyzed 80 patients retrospectively in the present study. The median age of patients was 64 years (range, 49–77).

Pathological examination was performed only for primary tumors, and determination of nodal involvement was predominantly based on imaging modalities. All patients underwent chest computed tomography (CT), and 41 patients (51%) underwent FDG-PET or FDG-PET/CT in addition prior to the initiation of treatment. LN involvement was defined as positive when its shortest diameter was 1 cm or greater on the chest CT and/or when discernible increase of FDG uptake (maxSUV > 2.0) was observed on FDG-PET/CT without inflammatory signs such as calcification (16). CT and FDG-PET were interpreted by an experienced radiologist with 20 years of experience and a nuclear medicine physician (Jin Mo Goo with 20 years of experience, and Jin Chul Paeng with 12 years of experience). Staging of primary tumors and nodal disease were based on the American Joint Committee on Cancer (AJCC) cancer staging manual, sixth edition (published in 2002).

Fifty patients were treated with IFI including only clinically identifiable tumors, and FDG-PET or FDG-PET/CT was performed in 54% of these patients (27/50). The other 30 patients were treated with ENI, and 47% of these patients (14/30) underwent PET-based staging. We specifically defined ENI as the following three situations: RT volume includes (1) uninvolved contralateral mediastinal and/or supraclavicular LN(s) in N2/3 disease or (2) uninvolved ipsilateral mediastinal and/or supraclavicular LN(s) in N1 disease or (3) ipsilateral mediastinal and/or contralateral mediastinal LN(s) in node-negative disease. Delivery of incidental radiation doses to different level of contralateral LN(s) in N3 disease with the object of covering involved ipsilateral LN(s) was not regarded as elective irradiation. The decision to treat with IFI or ENI was based on the treatment philosophy of radiation oncologists. Characteristics of the patients and tumors are summarized in Table 1 and are compared between the IFI and ENI groups. No significant differences were observed in clinical factors including age, performance status, T stage, N stage, radiation dose and sequence of chemotherapy between the groups.

Table 1.

Patient and treatment characteristics

  No. of patients (%)
 
P value 
IFI group (n = 50) ENI group (n = 30) 
Sex 
 Male 41 (82) 26 (87) 0.757 
 Female 9 (18) 4 (13)  
Age (years) 
 Median (range) 64 (50–77) 62 (49–76) 0.424 
ECOG performance status 
 0 8 (16) 2 (7) 0.460 
 1 40 (80) 27 (90)  
 2 2 (4) 1 (3)  
T stage 
 0/1 11 (22) 8 (27) 0.970 
 2 21 (42) 12 (40)  
 3 5 (10) 3 (10)  
 4 13 (26) 7 (23)  
N stage 
 0 8 (16) 7 (23) 0.729 
 1 2 (4) 2 (7)  
 2 26 (52) 15 (50)  
 3 14 (28) 6 (20)  
Overall stage 
 IA 1 (2) 1 (3) 0.923 
 IB 6 (12) 4 (13)  
 IIA 2 (4) 2 (7)  
 IIB 1 (2) 1 (3)  
 IIIA 19 (38) 13 (44)  
 IIIB 21 (42) 9 (30)  
PET staging 
 Yes 27 (54) 14 (47) 0.525 
 No 23 (46) 16 (53)  
RT dose 
 Median (Gy) (range) 54 (44–64) 54 (40–65) 0.516 
 <54 Gy 11 (22) 8 (27) 0.637 
PCI 
 Yes 36 (72) 23(77) 0.646 
 No 14 (28) 7 (23)  
Chemotherapy regimen 
 Etoposide/cisplatin 40 (80) 27 (90) 0.351 
 Etoposide/carboplatin 10 (20) 3 (10)  
Chemotherapy cycle 
 Median (range) 6 (3–8) 6 (2–6) 0.509 
 Less than six cycles 5 (10) 3 (10) 1.000 
Chemotherapy-RT sequence 
 Early concurrent 25 (50) 20 (67) 0.252 
 Late concurrent 11 (22) 6 (20)  
 Sequential 14 (28) 4 (13)  
Initial response 
 Complete response 19 (38) 19 (64) 0.170 
 Partial response 24 (48) 10 (30)  
 Stable 3 (6) 0 (0)  
 Progression 4 (8) 1 (3)  
  No. of patients (%)
 
P value 
IFI group (n = 50) ENI group (n = 30) 
Sex 
 Male 41 (82) 26 (87) 0.757 
 Female 9 (18) 4 (13)  
Age (years) 
 Median (range) 64 (50–77) 62 (49–76) 0.424 
ECOG performance status 
 0 8 (16) 2 (7) 0.460 
 1 40 (80) 27 (90)  
 2 2 (4) 1 (3)  
T stage 
 0/1 11 (22) 8 (27) 0.970 
 2 21 (42) 12 (40)  
 3 5 (10) 3 (10)  
 4 13 (26) 7 (23)  
N stage 
 0 8 (16) 7 (23) 0.729 
 1 2 (4) 2 (7)  
 2 26 (52) 15 (50)  
 3 14 (28) 6 (20)  
Overall stage 
 IA 1 (2) 1 (3) 0.923 
 IB 6 (12) 4 (13)  
 IIA 2 (4) 2 (7)  
 IIB 1 (2) 1 (3)  
 IIIA 19 (38) 13 (44)  
 IIIB 21 (42) 9 (30)  
PET staging 
 Yes 27 (54) 14 (47) 0.525 
 No 23 (46) 16 (53)  
RT dose 
 Median (Gy) (range) 54 (44–64) 54 (40–65) 0.516 
 <54 Gy 11 (22) 8 (27) 0.637 
PCI 
 Yes 36 (72) 23(77) 0.646 
 No 14 (28) 7 (23)  
Chemotherapy regimen 
 Etoposide/cisplatin 40 (80) 27 (90) 0.351 
 Etoposide/carboplatin 10 (20) 3 (10)  
Chemotherapy cycle 
 Median (range) 6 (3–8) 6 (2–6) 0.509 
 Less than six cycles 5 (10) 3 (10) 1.000 
Chemotherapy-RT sequence 
 Early concurrent 25 (50) 20 (67) 0.252 
 Late concurrent 11 (22) 6 (20)  
 Sequential 14 (28) 4 (13)  
Initial response 
 Complete response 19 (38) 19 (64) 0.170 
 Partial response 24 (48) 10 (30)  
 Stable 3 (6) 0 (0)  
 Progression 4 (8) 1 (3)  

IFI, involved-field irradiation; ENI, elective nodal irradiation; ECOG, eastern cooperative oncology group; PET, positron-emission tomography; RT, radiotherapy; PCI, prophylactic cranial irradiation.

Treatment

For RT planning, contrast-enhanced CT was performed with a maximal slice thickness of 5 mm. Gross tumor volume (GTV) was delineated based on the assessment of abnormalities in the post-chemotherapy CT scans. For IFI treatment planning, the margin from the GTV to the clinical target volume (CTV) was 5 mm and from the CTV to the planning target volume, it was 5 mm for nodal areas and 10–15 mm for the primary lung tumor according to tumor motion, which was judged by X-ray fluoroscopy. For ENI treatment planning, CTV included GTV, as described above, and clinically uninvolved LNs such as ipsilateral hilum, mediastinum and the supraclavicular area (only for patients with the superior mediastinal LN involvement).

Three-dimensional planning was used with a XiO treatment planning system (Computerized Medical System, St Luis, MS, USA). The median radiation doses were 54 Gy (range, 44–64 Gy) for primary tumor/involved LNs and 44 Gy for ENI. RT was delivered once daily 5 days a week with a fraction size of 2 Gy, given concurrently (77%) or sequentially (23%) with chemotherapy. Concurrent chemoradiotherapy was divided into early (within the third cycle) or late (fourth cycle or later) according to the cycle in which the two modalities were combined. Chemotherapy regimens consisted of etoposide (100 mg/m2/day on Days 1–3) and cisplatin (70 mg/m2/day on Day 1) or carboplatin (AUC 5 on Day 1), administered intravenously every 3 weeks for six cycles. Prophylactic cranial irradiation consisting of 25 Gy in 10 fractions was delivered to patients who achieved complete or partial response in about a month after completion of treatment.

Follow-up

After completion of treatment, patients underwent physical examination, laboratory tests, chest radiography, chest CT and/or FDG-PET/CT every 2–3 months in the first year and every 3–6 months thereafter. Bone scans or brain MRIs were performed at any time upon suspicion for metastasis. The median duration of follow-up was 25 months (range, 5–82) for all patients and 33 months (range, 6–82) for the survivors.

Statistical Analysis

Overall survival (OS) and progression-free survival (PFS) were calculated from the date that definitive treatment was initiated. INF was defined as recurrence in initially uninvolved LNs in the absence of distant metastasis. Radiation-induced pneumonitis and esophagitis were graded according to the Common Terminology Criteria for Adverse Events v3.0 criteria.

We performed statistical analysis using Statistical Package for Social Sciences software (SPSS Statistics; version 17.0, SPSS Inc., Chicago, IL, USA). The distribution of clinical factors was evaluated by χ2 test or Fisher's exact test. The actual survival rates were estimated by the Kaplan–Meier method, and the difference in survival was evaluated by log-rank test. Uni-/multi-variate analyses were performed with the Cox proportional hazard model. A P value of <0.05 was regarded as statistically significant.

RESULTS

Treatment Outcomes

At the last follow-up, 41 of 80 patients died. Causes of death were disease progression in 37 patients, intercurrent disease (acute myocardial infarction and intracranial hemorrhage) in 2 and unknown for the remaining 2 . Ten patients were alive with the disease, and 29 were alive with no evidence of disease. Among these, two patients who experienced local failure only regained complete remission after salvage surgery.

The 3 year OS of the IFI and ENI groups were 44.6 and 54.1% (P= 0.220), and the 3 year PFS were 24.2 and 42.8% (P= 0.133), respectively (Fig. 1). For patients who underwent PET-based staging, the 3 year OS (53.7 vs. 52.1%, P= 0.962) and the 3 year PFS (33.2 vs. 32.1%, P= 0.853) were not different between the both groups (Fig. 2). On the other hand, for patients who did not undergo PET scans, the 3 year OS (29.3 vs. 56.3%, P= 0.022) and the 3 year PFS (11.0 vs. 50.0%, P= 0.040) were significantly longer in the ENI group (Fig. 3).

Figure 1.

Survival curves for overall patients are demonstrated according to radiotherapy (RT) extent: (a) overall survival (OS), (b) progression-free survival (PFS). ENI, elective nodal irradiation; IFI, involved-field irradiation.

Figure 1.

Survival curves for overall patients are demonstrated according to radiotherapy (RT) extent: (a) overall survival (OS), (b) progression-free survival (PFS). ENI, elective nodal irradiation; IFI, involved-field irradiation.

Figure 2.

Survival curves for patients with PET implementation are demonstrated according to RT extent: (a) OS, (b) PFS. Abbreviations are as shown as in Fig. 1.

Figure 2.

Survival curves for patients with PET implementation are demonstrated according to RT extent: (a) OS, (b) PFS. Abbreviations are as shown as in Fig. 1.

Figure 3.

Survival curves for patients without PET implementation are demonstrated according to RT extent: (a) OS, (b) PFS. Abbreviations are as shown as in Fig. 1.

Figure 3.

Survival curves for patients without PET implementation are demonstrated according to RT extent: (a) OS, (b) PFS. Abbreviations are as shown as in Fig. 1.

Uni- and Multi-variate Analysis of Prognostic Factors for OS and PFS

In univariate analysis, advanced N stage and initial response less than CR were negatively associated with both OS and PFS and advanced T stage with PFS only (Table 2). In multi-variate analysis, OS was negatively associated with advanced N stage (P= 0.009) and initial response less than CR (P= 0.037), but risk factors for PFS were insignificant (Table 3). Omission of ENI and an initial PET scan were not independent predictors for OS and PFS.

Table 2.

Univariate analysis of prognostic factors

 HR for OS (95% CI) P value HR for PFS (95% CI) P value 
Age ≥70 vs. <70 0.749 (0.359–1.561) 0.440 0.499 (0.233–1.066) 0.073 
T stage 3–4 vs. 1–2 1.613 (0.880–2.956) 0.122 1.797 (1.027–3.143) 0.040 
N stage 2–3 vs. 0–1 3.638 (1.429–9.261) 0.007 2.203 (1.065–4.555) 0.033 
PET staging vs. CT staging 0.665 (0.361–1.224) 0.190 1.005 (0.577–1.751) 0.985 
ENI vs. IFI 0.605 (0.319–1.145) 0.123 0.640 (0.355–1.152) 0.136 
Early RT vs. late RT 1.084 (0.597–1.969) 0.791 1.238 (0.707–2.17) 0.455 
Initial CR vs. less than CR 0.530 (0.290–0.972) 0.040 0.533 (0.303–0.936) 0.028 
 HR for OS (95% CI) P value HR for PFS (95% CI) P value 
Age ≥70 vs. <70 0.749 (0.359–1.561) 0.440 0.499 (0.233–1.066) 0.073 
T stage 3–4 vs. 1–2 1.613 (0.880–2.956) 0.122 1.797 (1.027–3.143) 0.040 
N stage 2–3 vs. 0–1 3.638 (1.429–9.261) 0.007 2.203 (1.065–4.555) 0.033 
PET staging vs. CT staging 0.665 (0.361–1.224) 0.190 1.005 (0.577–1.751) 0.985 
ENI vs. IFI 0.605 (0.319–1.145) 0.123 0.640 (0.355–1.152) 0.136 
Early RT vs. late RT 1.084 (0.597–1.969) 0.791 1.238 (0.707–2.17) 0.455 
Initial CR vs. less than CR 0.530 (0.290–0.972) 0.040 0.533 (0.303–0.936) 0.028 

HR, hazard ratio; OS, overall survival; CI, confidence interval; PFS, progression-free survival; CT, computed tomography; CR, complete response.

Table 3.

Multi-variate analysis of prognostic factors

 HR for OS (95% CI) P value HR for PFS (95% CI) P value 
Age ≥70 vs. <70 1.075 (0.493–2.343) 0.856 0.606 (0.268–1.370) 0.228 
T stage 3–4 vs. 1–2 1.486 (0.803–2.752) 0.207 1.523 (0.850–2.728) 0.158 
N stage 2–3 vs. 0–1 3.739 (1.385–10.091) 0.009 1.748 (0.806–3.791) 0.157 
PET staging vs. CT staging 0.573 (0.304–1.077) 0.084 0.830 (0.462–1.494) 0.535 
ENI vs. IFI 0.891 (0.428–1.851) 0.756 0.839 (0.425–1.654) 0.611 
Early RT vs. late RT 1.102 (0.578–2.102) 0.767 1.071 (0.573–2.001) 0.830 
Initial CR vs. less than CR 0.496 (0.257–0.958) 0.037 0.552 (0.299–1.019) 0.058 
 HR for OS (95% CI) P value HR for PFS (95% CI) P value 
Age ≥70 vs. <70 1.075 (0.493–2.343) 0.856 0.606 (0.268–1.370) 0.228 
T stage 3–4 vs. 1–2 1.486 (0.803–2.752) 0.207 1.523 (0.850–2.728) 0.158 
N stage 2–3 vs. 0–1 3.739 (1.385–10.091) 0.009 1.748 (0.806–3.791) 0.157 
PET staging vs. CT staging 0.573 (0.304–1.077) 0.084 0.830 (0.462–1.494) 0.535 
ENI vs. IFI 0.891 (0.428–1.851) 0.756 0.839 (0.425–1.654) 0.611 
Early RT vs. late RT 1.102 (0.578–2.102) 0.767 1.071 (0.573–2.001) 0.830 
Initial CR vs. less than CR 0.496 (0.257–0.958) 0.037 0.552 (0.299–1.019) 0.058 

Abbreviations are as shown as in Table 2.

Patterns of Failure and INF According to the Implementation of FDG-PET

The most common pattern of initial failure was locoregional only in 36.7%, followed by distant only in 32.6% and locoregional plus distant in 30.7%. The crude incidence of INF was 6.0% (3/50) in the IFI group and 0% (0/30) in the ENI group, respectively. All three patients who experienced INF in the IFI group had not undergone PET scans as an initial work-up. One of three INFs developed in mediastinal LNs, another INF in combined mediastinal and supraclavicular LNs, and the remaining one in the supraclavicular LN only. The patterns of INF according to ENI and PET-based staging are summarized in Table 4. For patients who experienced INF, the median PFS was 10.0 months (range, 7.6–11.6 months). Salvage treatment seemed to be ineffective for patients who experienced INF. All patients died of disease progression accompanied by subsequent distant metastatic events (3/3) and/or local progression (2/3).

Table 4.

Patterns of INF according to the implementation of FDG-PET as initial work-up

  Incidence of INF
 
IFI group (n = 50) ENI group (n = 30) 
Without FDG-PET 3/23 0/16 
With FDG-PET 0/27 0/14 
  Incidence of INF
 
IFI group (n = 50) ENI group (n = 30) 
Without FDG-PET 3/23 0/16 
With FDG-PET 0/27 0/14 

INF, isolated nodal failure; FDG, 18F-fluorodeoxyglucose.

Treatment-Related Acute Toxicities

The overall incidence rate of Grade 2 or higher radiation-induced pneumonitis was 45% (36/80) and was more common in the IFI group (48 vs. 40%), but Grade 3 or higher pneumonitis was more frequently observed in the ENI group (13 vs. 10%). Similarly, patients in ENI suffered more from Grade 3 or higher esophagitis (13 vs. 10%). There were no significant differences in the incidence of pneumonitis and esophagitis between the two groups (P= 0.770). However, one patient in the ENI group experienced Grade 4 pneumonitis after treatment and had to be hospitalized, and another patient in the ENI group did not receive his planned dose because he refused further RT due to odynophagia from Grade 3 esophagitis.

DISCUSSION

A trend has recently developed toward gradual reduction in nodal RT target volume to minimize RT-related adverse events in the treatment for LS-SCLC (17). In trials published in the 1980s, extensive ENI was predominant. RT volume included the primary tumor, ipsilateral hilar LN, and bilateral mediastinal and supraclavicular LNs (1). In trials from the 1990s to early 2000s, a shift to selective ENI was observed, which means RT volume included the primary tumor, ipsilateral hilar LN, bilateral mediastinal LN and involved supraclavicular LN only (4,5,7–9). After that, the concept of IFI was introduced in CALGB 39808 and a Dutch multi-center phase II trial (10,11). In their studies, RT volumes were defined by restaging CT after induction chemotherapy, including only the primary tumor (post-chemotherapy) and clinically involved LNs with a short diameter of 1 cm or greater on CT (pre- and post-chemotherapy). However, few studies have reported the effect of the extent of nodal target volume on survival outcomes. We retrospectively analyzed survival outcomes according to the use of ENI, and no significant differences were observed in OS and PFS between the IFI and ENI groups.

As the role of TRT in the treatment of LS-SCLC is to improve locoregional control, it is important to assess whether the omission of ENI could influence INF or not. A retrospective study in which patients were treated with twice-daily IFI and concurrent chemotherapy reported that no isolated out-of-field mediastinal recurrence in the absence of supraclavicular or more distant disease was observed, but two INFs (combined mediastinal and supraclavicular) developed in patients who had not undergone FDG-PET for the initial staging (14). Also, Hu et al. (15) reported an exceptionally low risk (2.5%) of isolated out-of-field recurrent rate without ENI.

Recently, PET scans tend to be used routinely as a part of the staging work-up for SCLC. Although it is substantially difficult to validate the usefulness of FDG-PET with clinical results in SCLC because surgery is not a component of the definitive treatment modality for SCLC in contemporary practice, there are evidences for the utility of FDG-PET. Some have reported that the impact of FDG-PET on staging migration resulted in the alteration of RT planning in 12–25% (18–20). Also, a few studies have noted improved sensitivity and specificity of FDG-PET over CT in SCLC (21–23). Two prospective phase II trials from the Netherlands have directly addressed the issue of ENI omission for LS-SCLC according to the use of PET scans in the initial work-up. Even though IFI had been observed to increase risk of INF with a crude rate of 11% (3/27) at the first trial using CT staging alone (24), their subsequent trial in which all subjects were staged by FDG-PET revealed only a 3% (2/60) crude rate of INF (13). The results were comparable with that of our study, in which INF were observed in eight in the IFI group and 3% in the ENI group. More importantly, no out of field failure was observed with the implementation of PET scans.

van Loon et al. (25) pointed out the possibility that relatively low rates of INF with IFI may result from incidental radiation doses delivered to regional LN areas. A recently published planning study showed that IFI with FDG-PET/CT staging improved tumor coverage and reduced the organs-at-risk dose without compromising coverage for the next echelon LN, suggesting the possibility of dose escalation (26). Also, Shirvani et al. (27) reported that FDG-PET/CT-guided IFI, even using intensity-modulated RT, resulted in only one INF with a median follow-up of 21 months.

The incidence of acute toxicities in our study was relatively low compared with those of previously published studies, and the incidence of Grade 3 or higher pneumonitis and esophagitis was not significantly increased with ENI (7,28–31). Considering that SCLC has the preponderance of a central location, it may be well explained that reduction of RT volume by omitting ENI resulted in decreased RT-induced esophagitis. IFI might be considered preferentially to avoid acute morbidity, especially for elderly patients with low performance.

This study has some shortcomings. First, the decision between IFI and ENI was not randomly assigned from the fundamental limitation of the retrospective study. Recently, there has been a trend to favor IFI over ENI in our institute, which is based on the reflection from the result of numerous studies justifying the omission of ENI for NSCLC. Second, PET was not regarded as standard imaging modality for staging work-up in the early period of this study. The implementation of PET was decided by physicians who underwent diagnostic work-up. This arbitrary decision might lead selection bias. Finally, the timing of RT was not suitable considering the recent evidence favoring early initiation of RT (32,33). A substantial proportion (42.5%) of patients received RT concurrently after three cycles of chemotherapy or even sequentially after the completion of chemotherapy.

CONCLUSIONS

This retrospective study of 80 patients with LS-SCLC demonstrated that the omission of ENI did not compromise OS and PFS significantly. However, if patients did not undergo PET-based staging, the omission of ENI resulted in impaired survival outcomes and raised the risk of INF. Therefore, IFI might be reasonable only with PET scan implementation.

Conflicts of interest statement

None declared.

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