PowerPoint presentation on management of small cell lung cancer.

1. Small Cell Lung Cancer
Management
Dr.Tinku Joseph
DM Resident
Department of Pulmonary medicine
AIMS, Kochi

2. INTRODUCTION
 Typically arise centrally
 Most common presentation is a large hilar mass with
bulky mediastinal LN
 Common symptoms cough, SOB, wt loss.
 Commonly seen in smokers.
 Approx. 70 % with overt mets at presentation
 Commonly spread to liver, adrenals, bone and brain
 Can present with paraneoplastic syndome.

3. • SCLC Incidence:
– 13% of all lung CA
INTRODUCTION

4. Natural History of SCLC
 SCLC is distinguished from NSCLC by its rapid
doubling time, high growth fraction, and the early
development of widespread metastases
 considered highly responsive to chemotherapy and
radiotherapy, SCLC usually relapses within two years
despite treatment
 Overall, only three to eight percent of all patients
with SCLC (10 to 13 percent of those with limited
disease) survive beyond five years

5. SCLC Histology
 SCLC is a “small blue round cell tumor” from
neuroendocrine cells
 Classifications:
- oat cell (lymphocyte-like), fusiform, polygonal
- OR classical, large cell neuroendocrine, combined
SCLC/NSCLC

6. STAGING

7. Staging of small cell lung cancer

10. STAGING

11. DEFINITION OF DISEASE EXTENSION
• Very-limited disease: confined to one hemithorax
without mediastinal lymph node involvement.
• Limited disease: confined to one hemithorax
including the contralateral lymph nodes (all within
radiation field).
• Extensive disease: beyond these bounderies.

12. Where does SCLC metastasize to?
“BALLS”
 Brain (30%)
 Adrenal (20-40%)
 Liver (25%)
 Lung
 Skeleton (35%)

13. survival of SCLC
Marginally improvement of survival in 2 decades
Limited Disease (Janne et al.
Cancer 2002)
Median survival SEER database
Extensive Disease (Chute et al. J
Clin Oncol 1999)

14. Approach to very-limited
disease
Surgery followed by chemotherapy

15. Survival of patients with SCLC according to
lymph node involvement
pTN1M0 (n=51)
pTN2M0 (n=32)
Eur J Cardiothorac Surg, 5:306;1991
pTN0M0 (n=63)

16. About half of patients with very-limited disease
may be cured with combined-modality
approach that includes surgical resection and
adjuvant chemotherapy

17. Limited Section Disease (LS-SCLC)
 Definition-: disease that is limited to the ipsilateral
hemithorax and regional lymph nodes and can be
encompassed in a safe radiotherapy field.
 Most cases-: clinical or pathologic evidence of
mediastinal lymph node disease.

18.  For patients with LS-SCLC who have no distant
metastases, no evidence of disease in the
mediastinum, and no other contraindications to
surgery, resection is indicated.
 Followed by adjuvant chemotherapy with four cycles
of cisplatin-based therapy.
Limited Section Disease (LS-SCLC)

19.  For patients in whom surgery identifies lymph node
involvement in the pathologic specimen,
chemoradiotherapy is generally indicated.
 For most patients with LS-SCLC who have clinical or
pathologic evidence of mediastinal disease,
chemoradiotherapy is indicated as the initial
treatment.
Limited Section Disease (LS-SCLC)

20. Chemotherapy for
Small Cell Lung Cancer -LS

21.  Four cycles of chemotherapy is the mainstay of
treatment for patients with LS-SCLC.
 High frequency of early dissemination.
Limited Section Disease (LS-SCLC)

22.  In addition to chemotherapy, there is a significant
role for radiation therapy (RT) in the treatment of LS-
SCLC.
 Local tumor progression occurs in up to 80 % of such
patients treated with chemotherapy alone.
 High local recurrence rate can be significantly
reduced by the addition of thoracic RT.
 Survival is improved when thoracic RT is added to
chemotherapy compared with chemotherapy alone
Limited Section Disease (LS-SCLC)

23.  Prophylactic cranial irradiation
 Indicated for patients with a complete or
partial response to their initial chemotherapy
treatment.
Limited Section Disease (LS-SCLC)

24.  SCLC and symptoms of superior vena cava (SVC)
obstruction, initial chemotherapy is the treatment of
choice, rather than RT.
 The clinical response to chemotherapy alone is
usually rapid.
 RT may be required for patients in extreme distress
due to SVC obstruction or in those who do not
respond to chemotherapy.
Limited Section Disease (LS-SCLC)

25. Benefit of treatment
 Patients with SCLC rarely survive more than a few
months without treatment, even when disease
appears to be localized.
 SCLC is highly responsive to both multiple
chemotherapeutic drugs and radiation therapy (RT).
 The results with treatment vary significantly
depending upon the extent of disease.

26.  Treated with contemporary chemoradiotherapy and
prophylactic cranial irradiation-: overall response
rates of 80 to 90 percent, including 50 to 60 percent
complete response rates.
 Median survival is around 17 months, and the five-
year survival rate is about 20 percent
Benefit of treatment

27. CHEMOTHERAPY- LS-SCLC
 Current standard of care for patients with LS-SCLC:
Four cycles of combination chemotherapy (typically
cisplatin plus etoposide [EP]) + concurrent thoracic
radiotherapy during the early part of the
chemotherapy treatment.
 Prophylactic cranial irradiation (PCI) is generally
recommended for patients with a complete response
or significant tumor regression at the completion of
chemotherapy.

28. Prophylactic cranial irradiation (PCI)

29. Chemotherapy regimens
• Etoposide + Cisplatin
• standard regimen for chemotherapy in patients with
LS-SCLC along with early, concurrent thoracic
radiotherapy.
• Alternative-: Etoposide + carboplatin
• Neuropathy, hearing loss, renal insufficiency, CCF

31. Other regimens
 Irinotecan-containing regimens
 Paclitaxel-containing regimens
 Novel agents
 Tirapazamine, thalidomide, vandetanib,
bevacizumab, matrix metalloproteinase inhibitors ,
tamoxifen, and the Bec2/BCG vaccine.

32. THORACIC RADIATION THERAPY
 Improvement in survival
 Increase in toxicity.
 conventional (once daily) fractionation use doses of
approximately 60 to 70 Gy in 2 Gy fractions.
 Split course treatment alternating regimens of
chemotherapy and thoracic RT.

33. PROPHYLACTIC CRANIAL
IRRADIATION
 Decrease the incidence of symptomatic brain
metastases and increase overall survival in patients
with limited stage small cell lung cancer.
 INTEGRATION WITH CHEMOTHERAPY — The
addition of thoracic radiation therapy (RT) integrated
with etoposide plus cisplatin (EP) chemotherapy
during cycle 1 or 2 is the current standard of care for
patients with LS-SCLC.

34. SCLC - Meta-analysis of PCI
From 7 randomised trials of PCI vs no-PCI
Patients 987 (140 patients had ED-SCLC)
Chemo- & RT schemes various
Overall survival benefit +5% (95% CI: 1 -10%)
3 year survival 20 vs 15%
Incidence of brain metas 33 vs 59%
Auperin et al. NEJM 1999

35. Early versus late thoracic RT
 conflicting data
 Early (starting with cycle 1 or 2 of chemotherapy)
rather than late integration of thoracic RT is
associated with a better outcome.
A meta-analysis reported in 2004, A 2005 Cochrane meta-analysis,
trial from the National Cancer Institute of Canada (NCIC)

37. Approach to SCLC - ES

38. SCLC - ES
 The majority of patients with SCLC have extensive
stage disease.
 Definition-: tumor that includes distant metastases,
malignant pericardial or pleural effusions, and/or
contralateral supraclavicular or contralateral hilar
lymph node involvement.
 primary therapeutic modality is systemic
chemotherapy.
 Good response to chemotherapy-: RT additional
benefit.

39.  Prophylactic cranial irradiation-: decreases the
incidence of symptomatic brain metastases in
patients who have responded to systemic
chemotherapy.
 Impact on overall survival is uncertain
SCLC - ES

41.  Cisplatin + Etoposide-: Most frequently used.
 Carboplatin + Etoposide
 Cisplatin + Irinotecan-: Favourable results
Japanese Cooperative Oncology Group trial (JCOG 9511)
 Topotecan plus cisplatin
 Epirubicin plus cisplatin
 Three or four-drug combinations -: Added paclitaxel (not
favourable results)
SCLC - ES

42. • Duration of therapy-: four to six cycles of induction
therapy.
• RADIATION THERAPY AFTER RESPONSE TO
CHEMOTHERAPY
• Thoracic RT is associated with improved overall
survival.
• Prophylactic cranial irradiation -: decrease the
incidence of symptomatic brain metastases
SCLC - ES

46. SCLC-: In Elderly
 ELDERLY PATIENTS -: one-third of patients with SCLC
are 70 years of age or older.
 Standard regimens-: Increased toxicity.
 Trials conducted -:Response rate was higher with full
doses compared with the low dose

47. POOR PERFORMANCE STATUS PATIENTS

48.  No data that define the role of treatment in poor
performance status patients (PS3 or PS4).
POOR PERFORMANCE STATUS
PATIENTS

49. Median survivals in SCLC
 Very-limited disease ~5 years
 Limited disease 18-24 months
 Extensive disease 10 months
 SCLC without treatment < 3 months

50. Prognostic Factors
 The host factors of poor performance status and
weight loss
 Stage (limited versus extensive).
 In extensive disease-: the number of organ sites
involved.
 Metastatic involvement of the central nervous
system, the marrow, or the liver is unfavorable
compared to other sites.
 Most trials-: women fare better than men,
 Presence of paraneoplastic syndromes is generally
unfavorable

51. Experimental Approaches- SCLC
 ANGIOGENESIS INHIBITORS
 Oral angiogenesis inhibitors - Tyrosine kinase (TK) inhibitors
sorafenib, sunitinib, cediranib, vandetanib.
 Bevacizumab has been studied in combination with platinum-
based chemotherapy
 Topotecan, Thalidomide.
 IGF-1R inhibitors-: Cixutumumab
 IMMUNOTHERAPY
 Tumor vaccines anti-idiotypic antibody (BEC-2)
 CYTOTOXIC CHEMOTHERAPY-: Bendamustine

52. ACCP GUIDELINES
NATIONAL COMPREHENSIVE CANCER
NETWORK (NCCN)
NICE GUIDELINES FOR LUNG CANCER