Definition: Small cell lung carcinoma (SCLC) is a type of lung cancer that typically starts in the bronchi (large airways) and tends to grow and spread quickly. It accounts for approximately 10-15% of all lung cancers. Characteristics: SCLC is characterized by small, oat-shaped cancer cells that rapidly divide and form large tumors. It is often associated with a history of smoking and has a strong correlation with tobacco exposure. Aggressive nature: SCLC is considered highly aggressive, with a tendency to metastasize (spread) early to the lymph nodes and other distant parts of the body, such as the liver, bones, and brain. This rapid spread makes early detection and treatment crucial. Limited and extensive stage: SCLC is classified into two stages: limited stage and extensive stage. Limited stage means the cancer is confined to one side of the chest and potentially adjacent lymph nodes, whereas extensive stage indicates that the cancer has spread beyond the chest to distant organs. Treatment approach: The treatment of SCLC typically involves a combination of chemotherapy and radiation therapy. Surgery is generally not recommended for SCLC due to its aggressive nature and tendency to spread early. Chemotherapy, often in combination with immunotherapy, is the mainstay of treatment and can help shrink tumors and control the disease. Prognosis: The prognosis for SCLC is generally poorer compared to non-small cell lung carcinoma (NSCLC) due to its more aggressive behavior and earlier metastasis. However, treatment advances and research efforts continue to improve outcomes for SCLC patients. Supportive care: As with any cancer diagnosis, supportive care plays a critical role in managing SCLC. This includes addressing symptoms, managing pain, providing emotional support, and ensuring optimal quality of life for patients. It's important to consult with healthcare professionals for an accurate diagnosis, personalized treatment plan, and ongoing monitoring for individuals suspected or diagnosed with small cell lung carcinoma.

1. Limited-stage small cell lung cancer: Initial
management
DR SUMIT KUMAR, ASSISTANT PROFESSOR, NEIGRIHMS

2. INTRODUCTION
SCLC is a poorly differentiated NET that represents approximately 15% of all lung cancers.
Nearly all patients with SCLC are current or former smokers.
Clinical characteristics are quick doubling time, high growth fraction, and the onset of metastases early on.
SCLC typically presents with widespread disease, necessitating systemic therapy as the primary approach..
Limited-stage SCLC often involves radiation therapy for thoracic disease and brain prophylaxis.
In rare cases of a single pulmonary nodule, surgery may be part of the treatment.
Extensive-stage SCLC is primarily treated with chemotherapy and immunotherapy.
Chest and brain radiation therapy may be considered in specific ES –SCLC cases.

3. Treatment flow chart
Small cell lung cancer on biopsy or FNAC of primary/metastatic site
Extensive stage
Cect –chest+abd.+pelvis/Brain mri or Whole body PET/CT
Limited stage
PFT/Bone scan /BMA-if no PET
Limited stage
(T1-T2NOMO
Limited
(IIB-IIIC)
BMB
Consistent with
malignancy
Pathologic mediastinal staging
negative
Medically inoperable Pathologic mediastinal staging
positive
Lobectomy& mediastinal
LND SABR CTRT
R0 R1/R2
CTRT
CT CT

9. DEFINITION OF LIMITED-STAGE DISEASE
 LS-SCLC is defined as disease that is limited to the ipsilateral hemithorax and
regional lymph nodes and can be encompassed in a safe radiotherapy field.
 Most patients with LS-SCLC will have clinical or pathologic evidence of mediastinal
lymph node involvement.
 For staging following test to be done :
 CECT of chest, abdomen, and pelvis.
 PET-CT-whole body/MRI of the brain (CT brain with contrast if MRI is contraindicated).
 Bone scan (only if PET-CT is not available).
 Patients who have pleural effusions but otherwise LS disease should undergo
thoracentesis with cytologic analysis to confirm LS disease.

10. OVERVIEW OF TREATMENT AND BENEFITS
 The current standard of care for patients with LS-SCLC that involves the lymph nodes
consists of 4 cycles of combination chemotherapy (typically cisplatin plus etoposide [EP])
along with concurrent thoracic radiotherapy during the early part of the chemotherapy
treatment (starting with the 1st or 2nd cycle of chemotherapy).
 Prophylactic cranial irradiation (PCI) in CR or significant tumor regression at the completion
of chemotherapy.
 Carboplatin can be substituted if cisplatin is contraindicated for reasons such as pre-existing
neuropathy, hearing loss, renal insufficiency, or congestive heart failure.
 SCLC is highly responsive to both chemotherapy and radiation therapy.
 For patients with LS-SCLC treated with contemporary chemoradiotherapy and PCI, ORR of
80 to 90%, including 50 to 60% complete response rates, are typically reported.
 Median survival is approximately 17 months, and the 5-yr survival rate is approximately 20%.

11. STAGE I DISEASE (T1 to T2, N0)
 IF histologically hilar and mediastinal lymph nodes are not involved & no contraindications to surgery,
resection of the primary tumor with lobectomy, plus mediastinal lymph node sampling or dissection.
 Adjuvant chemotherapy with four cycles of cisplatin-based therapy.
IASLC database
Over 8000 cases of SCLC
349 cases (4 %) underwent surgery and staged
pathologically
 Reported 5-yr survival rates for
pathologic stages I, II, and III
SCLC: 48%, 39%, and 15%,
respectively.
National Cancer Database Analysis:
29,994 clinical stages I to III SCLC cases
compare 2,089 patients who had surgery with
nonsurgically treated patients.
Contrasted with clinical trial data showing a 5-yr survival
rate of 26% to 34% for primarily stage III SCLC with
nonsurgical (chemoradiotherapy) treatment.
 Nearly doubled median OS for N0
patients treated with surgery (38 vs. 22
months).
Favoured lobectomy over sublobar
resections and pneumonectomies

12. Postoperative chemotherapy —
Study/Analysis Patient Group Adjuvant Treatment 5-Year Survival Rate
National Cancer Database
Study
Early-stage (pT1-2N0M0)
SCLC
Adjuvant Chemotherapy
(with or without
radiation)
Surgery Alone
53%
40%
Surgical Resection Series Patients who underwent
surgical resectionfor SCLC
(Pathologic Stages I-III)
Adjuvant Chemotherapy Stage I: 51%
Stage II: 28%
Stage III: 19%
Contrast with Earlier Studies Surgery Alone 1%
National Cancer Database
3017 patients with LS-SCLC
postoperative thoracic radiation therapy
5-year OS
N2 disease (29 vs 19 %)
N1 disease , no
differences
Study on Adjuvant Radiation Therapy (RT) in LS-SCLC with Nodal Involvement

13. STAGE II TO III DISEASE
Chemotherapy
 Initial studies of combined-modality therapy in patients with LS-SCLC used chemotherapy regimens such
as cyclophosphamide, doxorubicin, and vincristine (CAV), followed sequentially by thoracic RT.
146 patients with LS-SCLC received thoracic RT
(40 to 50 Gy) after four cycles of chemotherapy.
randomly assigned to CAV, EP, or CAV alternating
with EP
Outcome CAV EP, CAV
alternating
with EP
Response rates 51 % 77 % 88 %
overall survival
(OS) mth
12.4 11.7 11.8
myelotoxicity less
thoracic RT (42 Gy) was given between
the third and fourth cycles of
chemotherapy
EP compared with CEV)
OUTCOME EP CE
V
Median
survival(mth)
14.5 9.7
2-year survival
rates
25% 8 %
214 patients with LS-
SCLC
Etoposide plus cisplatin (EP) is the standard regimen for chemotherapy in patients with LS-SCLC along with early,
concurrent thoracic radiation therapy (RT

14. Substitution of carboplatin for cisplatin
Meta-analysis that included 663 patients in four trials compared
the efficacy of cisplatin-based versus carboplatin-based regimens
in SCLC
 Overall, response rate, PFS, and OS
were similar patients with both LS- and
ES-SCLC
 Hematologic toxicity was greater with carboplatin
 Nonhematologic toxicity was greater with cisplatin.
Cisplatin remains the standard agent, with carboplatin restricted to patients with contraindications to or poor
tolerance of cisplatin

15. Irinotecan-containing regimens
Phase III trial (JCOG0202),
256 patients without progression were randomly assigned to
consolidation with either irinotecan plus cisplatin or etoposide plus
cisplatin
281 patients were initially treated with induction etoposide plus
cisplatin in conjunction with accelerated hyperfractionated RT
No statistically significant difference in OS,

16. IRINOTECAN-CONTAINING REGIMENS
Paclitaxel-containing regimens
Two larger phase II
studies
evaluated TEP over standard EP plus
 did not demonstrate any improvement in efficacy
 grade 3 to 4 esophagitis in 32 to 36 % of
patients.

17. IRINOTECAN-CONTAINING REGIMENS
Novel agents
Tirapazamine
Thalidomide,
Vandetanib
Bevacizumab
Tamoxifen

18.  The addition of thoracic radiation therapy (RT) to chemotherapy results in a small, statistically significant
improvement in survival compared with the use of chemotherapy alone.although the combined-modality
approach is associated with an increase in toxicity.
 Two large meta-analyses have reported benefit to the use of combined chemotherapy and thoracic RT.
 One meta-analysis, which included 11 randomized studies, found that the addition of thoracic RT was
associated with an absolute improvement in local control of 23 percent (two-year local control rate, 47 versus
24 percent). The chemotherapy regimens differed among the studies, as did the thoracic RT doses and
delivery schedules.
 Another meta-analysis of 13 randomized trials (including the same 11 studies evaluated in the previously
noted meta-analysis) found that the use of combined chemotherapy and thoracic RT resulted in an absolute
survival benefit of 5.4 percent at three years.
 The survival benefit associated with the use of thoracic RT outside of clinical trials was also suggested in a
subsequent review from the National Cancer Database. For patients with LS-SCLC, the five-year survival rate
for the 6752 patients diagnosed in 2000 was significantly higher in patients treated with thoracic RT plus
chemotherapy compared with chemotherapy alone (13.3 versus 5.7 percent).
 While the benefit of RT in one of the meta-analyses was greatest for patients younger than 55 years old, with
a trend towards detriment in patients age 70 years and older, modern RT techniques and supportive care
have improved such that the benefits may outweigh toxicities for the older population as well. A retrospective
analysis of approximately 8600 patients age 70 years and older treated between 2003 and 2011 found that
the addition of RT to chemotherapy was associated with improved OS rates (15.7 percent absolute OS benefit
at three years).
Thoracic RT
Study Title/Source Number of Randomized Studies/no pt. Key Findings
Meta-Analysis 1 11
- Addition of thoracic RT associated with a
23% absolute improvement in local control
(two-year local control rate, 47% vs. 24%).
Meta-Analysis 2
13 Included the same 11 studies from
Meta-Analysis 1.
- Combined chemotherapy and thoracic RT
resulted in a 5.4% absolute survival benefit at
three years.
National Cancer Database
Review
For LS-SCLC patients diagnosed in 2000,
- 5-year survival rate was significantly higher in
patients treated with thoracic RT plus
chemotherapy compared to chemotherapy
alone (13.3% vs. 5.7%).
Retrospective Analysis of
Patients Age 70 and Older
(2003-2011)
Approximately 8600
- Addition of RT to chemotherapy associated
with a 15.7% absolute OS benefit at three
years.

19.  Treatment volume —limited-field thoracic RT is the current standard of care.
 All gross disease present at the time of RT planning (postchemotherapy volume), and all nodal regions
involved at the time of initial diagnosis (prechemotherapy volume).
 PET-CT scans should be obtained for staging if RT is planned for patients with suspected LS-SCLC
Thoracic RT : Treatment volume
trial by SWOG
191 patients with a partial response or stable
disease following induction chemotherapy,
Prechemotherapy tumor volumes Postchemotherapy tumor volumes
 No apparent difference in severe drug- related toxicity or radiation
pneumonitis
 Myelosuppression than the reduced-field group (18 versus 7 percent)
RT FIELD

20.  Preffered Regimen —45 Gy given in 1.5 Gy fractions twice daily over three weeks
 Alternate regimen- 60 to 70 Gy in fractions of 2 Gy once daily over 6-7 weeks
Thoracic RT : Dose fractionation schedule
Advantage of hyperfractionation
 Shorter total treatment time
 Potentially reduces the opportunity for tumor cell
regeneration
Toxicities
 More acute toxicities to normal tissues
 Late toxicities should be similar

21. Thoracic RT : Dose fractionation schedule (trial)
Trial Name Treatment Arm Response Toxicity
CONVERT trial(547 pt.)
Twice-daily RT (45 Gy/30 fractions) vs.
Once-daily RT (66 Gy/33 fractions)
Median survival: 30 vs. 25 months,
HR 1.18 (not statistically significant)
- Grade 3-4 esophagitis: 19% in
both groups .
Radiation pneumonitis: 3%vs. 2%
11 treatment-related deaths (3 in
BD group, 8 in OD group)
CALGB 30610 trial(638 pt.)
Twice-daily RT (45 Gy) vs. Once-daily RT (70
(70 Gy)
PFS: Median 13.5 vs. 14.2 months
OS: Median 29 vs. 31 months,
Similar rates of grade 3 or higher
adverse events in both arms
Phase III Trial (417 pt.)
Twice-daily RT (45 Gy) vs. Once-daily RT (45
(45 Gy)
- 5-year OS: 26% vs. 16% (twice-
daily better)
- Severe esophagitis: 27% (twice-
daily) vs. 11% (once-daily) -
No significant difference in severe
hematologic and pulmonary
toxicities
Randomized Phase II
Trial(182pt.)
Twice-daily RT (45 Gy/30 fractions) vs.
Once-daily RT (65 Gy/26 fractions)
- PFS: Median 13.4 vs. 17.2 months,
Median OS: 34 vs. 39 months (not
statistically significant)
Similar incidence of ≥grade 3
esophagitis and pneumonitis, and
treatment-related death rates in
both groups
Dose-Escalation Trial(170
pt.)
Dose-escalated RT (60 Gy/40 fractions) vs.
Standard RT (45 Gy/30 fractions)
- Improved 2-year OS rates: 75%
vs. 48%,
- No significant differences in local
control, PFS, distant metastasis end
No significant differences toxicity
rates.
In conclusion, the data support both 60 to 70 Gy daily RT or 45 Gy twice daily, with the possibility of escalating
the dose to 60 Gy twice daily, in select patients.

22. THORACIC RT : CONCURRENT VS SEQUENTIAL TREATMENT
 Preference for concurrent rather than sequential treatment —treatment start concurrently with
chemotherapy during cycle 1 or 2.
 However, concurrent or alternating regimens have been associated with more toxicity (myelosuppression,
esophagitis, pneumonitis) when compared with sequential treatment. This increased toxicity is considered
acceptable based on improved outcomes with concurrent regimens.
Trial Name/Source Treatment Approach Response Toxicity
Japanese Clinical
Oncology Group Study
9104
Concurrent VS
SequentialThoracic RT
Median OS: 27 vs. 20
months (not statistically
significant, p = 0.10)
- Severe esophagitis:
Concurrent group (9%),
Sequential group (4%)
- Similar rates of
pulmonary toxicity and
treatment-related death.
Meta-Analysis of 13
Randomized Trials
Sequential vs.
Alternating/Concurrent
Thoracic RT
No significant differences
in thoracic RT outcomes
between sequential and
alternating/concurrent
approaches.
Not specified (data on
specific toxicity rates and
outcomes not provided).

23. EARLY VERSUS LATE THORACIC RT
 Early versus late thoracic RT — We suggest that thoracic radiation therapy (RT) be integrated early
(in cycle 1 or 2) with chemotherapy rather than later in the treatment course.
 There have been eight randomized trials and three meta-analyses that have attempted to address the
timing of the delivery of thoracic RT relative to chemotherapy. All the studies that employed standard
cisplatin-based chemotherapy without significant dose reductions convincingly showed that early
(starting with cycle 1 or 2 of chemotherapy) rather than late integration of thoracic RT is associated with
a better outcome.
 As an example, a meta-analysis reported in 2004, which included seven randomized trials published
after 1985, showed a significant improvement in two-year OS for early versus late thoracic RT. A
subsequent meta-analysis showed that the most important factor associated with improved five-year
survival was a short interval between the start of any treatment and the completion of thoracic RT
(relative risk, 0.62).
 Is there a role for surgery in patients with a good response to treatment? —In the setting of limited
data, not pursue surgery in patients with stage II or III disease, irrespective of response to
chemoradiotherapy, although we acknowledge that other experts may adopt this approach in select
instances.
Study/Analysis Timing of Thoracic RT Key Findings
Meta-Analysis (2004) seven
randomized trials published after 1985
Early (cycle 1 or 2) - Significant improvement in two-year
OS for early vs. late thoracic RT.
Subsequent Meta-Analysis
Early (short interval between start of
any treatment and thoracic RT)
- Short interval between treatment
start and thoracic RT associated with
improved five-year survival (relative
risk, 0.62).

24. PROPHYLACTIC CRANIAL IRRADIATION
 Prophylactic cranial irradiation (PCI) following chemotherapy has been demonstrated to decrease the
incidence of symptomatic brain metastases (BM) and increase overall survival in patients with LS-SCLC
.
 As such, PCI is the standard of care for most patients with LS- SCLC who achieve a complete or good
partial response following treatment.

25. SPECIAL CONSIDERATIONS
 Patients with SVC obstruction — For patients with LS-SCLC and symptoms of superior vena cava
(SVC) obstruction, standard treatment should consist of concurrent chemotherapy plus definitive
thoracic radiation therapy (RT) with curative intent.
 If there is any potential delay in planning of RT, then the first cycle of chemotherapy should be initiated
as soon as possible, with definitive RT added in once planning has been completed.

26. SUMMARY AND RECOMMENDATIONS
 Introduction and treatment algorithm – A combined-modality approach is indicated for the
management of patients with limited-stage small cell lung cancer (LS-SCLC), following careful
staging to rule out distant metastases.
• For patients with clinical stage I (T1 to 2, N0) disease, invasive staging of mediastinal lymph
nodes is also indicated to identify the small fraction of patients who do not have lymph node
involvement or other metastatic disease.
• Stage I disease
• For patients with clinical stage I (cT1 to 2, N0) LS-SCLC, initial surgery followed by
adjuvant treatment
• If patients are not surgical candidates, chemoradiotherapy is an appropriate

27. SUMMARY AND RECOMMENDATIONS
• Stage II to III patients
• Chemotherapy – For patients with LS-SCLC four cycles of cisplatin plus
etoposide with concurrent RT
• Thoracic RT – Postchemotherapy gross disease and prechemotherapy
nodal volumes conventional fractionation (total dose of 60 to 70 Gy in
fractions of 2 Gy) or accelerated hyperfractionated schedules 45 Gy in twice-
daily fractions over three weeks concurrently with the first or second cycle of
chemotherapy.
• Prophylactic cranial irradiation – Prophylactic cranial irradiation is offered
to most patients with LS-SCLC who achieve a complete or very good partial
response to their initial chemotherapy treatment. Supporting data are
discussed elsewhere

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