SMALL CELL LUNG CARCINOMA Sthenjiswa Mhlongo Consultant: Prof A Sherriff 16/02/2019 University of Free State T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
DISCLOSURE • None T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
CASE • 50 year old male • Referred from Cardiothoracic Surgery • 3 months history of persistent cough T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
HISTORY • Main complaint: persistent cough for 3 months. Associated haemoptysis, voice hoarseness and occasional left chest pain. Weight loss. • Co-morbidities: HIV Negative. No known co-morbid diseases • Employed as truck driver • Social: strong smoking history - 30 pack year, social drinker • Family history: none of note T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
EXAMINATION • ECOG 1 • Hoarseness • No palpable nodes • Respiratory rate 19breath/min • Chest: not in respiratory distress. Decrease air entry on left lung field. Fine diffuse crepitations. • CVS: normal heart sounds • Abdomen: soft. No organomegaly • No neurological fallout T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
WORK UP • Lung biopsy: Small cell carcinoma. IHC was (+) for CK 7, TTF-1, synaptophysin & chromogranin. • Initial CXR: left upper lobe lung mass adjacent to superior left hilum. Left upper lobe consolidative chages + pleural thickening. Right lung fibrotic changes. • Bloods: – Full blood count with differential counts – Urea, electrolytes & creatinine – Sodium 133 – LDH 200U/L – Albumin 33 T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
PLAIN CHEST X-RAY T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
• Staging CT: Superior mediastinal mass 106 x 104mm, direct infiltration of left parasternal chest wall between the 2 nd & 3 rd rib ends anteriorly. Left brachiocephalic artery encasement. 12mm bronchopulmonary LN. 11mm pretracheal LN. Small left sided pleural effusion. Bilateral lung fibrosis. No metastatic disease • Cytology pleural effusion: no malignant cells. T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
CT IMAGING
BONE SCINTIGRAPHY Bone scintigraphy: increased uptake on left lateral aspect of manubrium and medial aspect of left 1 st rib. Direct sternum infiltration. No skeletal metastasis.
PROGNOSTIC FEATURES • Stage at presentation • Performance Status • Sex • weight loss > 5% over 6 Our patient’s poor prognostic months features: • Biochemical variables: • Male – Low sodium – ALP > 1,5x ULN • Weight loss >5% – LDH > ULN • LDH > upper limit of • Presence of normal paraneoplastic • Sodium < normal syndromes (controversial) • Continuation of smoking • Poor nutritional status
SUMMARY • 50 year old male SCLC limited stage • ECOG PS 1 • No comorbidities • Manchester scoring 2 • Poor prognostic features: – Male – Weight loss >5% – LDH > upper limit of normal – Sodium < normal T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
HIGHLY RESPONSIVE BUT ALSO HIGH RELAPSE RATES WITHIN 2 YEARS!! DESPITE OPTIMAL TREATMENT • Survival : – Limited stage: med OS 14-24months. 5yr OS 20% – Extensive stage: med OS 6-11 months. 5yr OS 2% – Shorter survival in untreated disease. • NB: para neoplastic syndromes at presentation may also influence patient clinical condition + management. Presence of paraneoplastic syndromes in generally unfavourable.
ROLE OF RADIATION • Role of thoracic radiotherapy is well established for LS – SCLC with marked improvement in OS • Early initiation of concurrent chemo radiation improves OS outcomes Optimal timing of radiation with 1 st or 2 nd cycle of chemotherapy • • Dose fractionation: – Hyper fraction vs standard fractionation – LC better with BD fractionation BUT OS very similar – Adverse effects esp. oesophagitis more frequent in BD fractionation • 3D conformal vs IMRT T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
DISCUSSION POINTS • Treatment options: – Optimum Dose Fractionation with concurrent chemotherapy: • 60- 70Gy/2Gy? • 45Gy/1,5Gy BD? – 3 D Conformal vs IMRT – Optimal timing of PCI
OUR MANAGEMENT • Concurrent chemo radiation • 54Gy in 2Gy fractions with concurrent Cisplatin and Etoposide • Restaging CT after completing adjuvant chemotherapy – Lung mass 56 x 61mm (106 x 104mm) – No measurable LN • Condition deteriorated to ECOG 2 , was still smoking heavily! • Not for PCI • For follow up T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
Thank You Ngiyabonga T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
• Staging: AJCC Staging Vs Veteran Administration Lung Study Group staging system • Highly responsive BUT also high relapse rates within 2 years!! Despite treatment • Clinical presentation • NB: para neoplastic syndromes • Work Up: include brain >30% patients present with brain mets at diagnosis • Common sites mets: Brain 30% > adrenal 20-30% > liver 25% > lung > bone • Survival : – Limited stage: med OS 14-24months. 5yr OS 20% – Extensive stage: med OS 6-11 months. 5yr OS 2% T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
CHEMO RADIATION • Benefit of adding XRT: Pigno meta-analysis – 13 trial, 2140pt. XRT 45-50Gy/20- 25#. Chemo CAV/MTX/VP16. 5% improvement in OS • Concurr vs Sequential (Japanese Clin Onc Group 9104): – n=231 – XRT 45Gy/1,5Gy BD + Cispl 80mg/m2 day 1 + Etop 100mg/m2 d1-3 – Concurr 4wkly chemo x 4 cycles begins XRT on day 2 of 1sst cycle chemo – med OS 27 months. 2yr OS 54% – Sequential q3w before start xrt x 4 cycles – med OS 20mnths. 2yr OS 35% • Early vs Late CCRT: – (1) NCIC study 1993. 308 pt randomized. XRT 45Gy in 15 # • Early Start XRT at #2 chemo( wk. 3): PFS 15,4 – med os 21,2 – 5yr OS 26% • Late start XRT at #6 chemo (wk. 15): PFS 11,8 – med OS 16 – 5yr OS 11% – (2) Jeremic Trial 1997. 107 pt. 54Gy in 1,5Gy BD. 4 x Carb+Etop & 4x Cisp+Etop. Carb with Xrt • Early RT wk. 1-4: med survival 34 months – 5yr OS 30% • Late RT wk. 6-9: med survival 26mnths – 5yr OS 15% T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
• Dose # – InterGrp 0096. 406pt . Randomized C-RT + PCI 25Gy • 45Gy/1,8Gy # OD + conc chemo in wk. 1. total chemo 4 x Cispl/Etop q3w LC 36% 5yr OS 18% • 45Gy /1,5Gy# BD + conc chemo in wk. 1. total chemo 4 x Cispl/Etop q3w LC 52% 5yr OS 26%. However gr 3 oesophagitis more frequent (27 vs 11%) • CRITISM!!! 45Gy OD not bio equivalent to 45gy BD – COVERT: hyper# + dose escalation for OS!! 4 x chemo Cispl/Etop. RT begins d22. DLY RT non inferior to BD RT!! • 45Gy/30# BD 2yr OS 56% • 66Gy/33 #OD 2yr OS 51% – CALGB30610/RTOG 0538 – PENDING • (A) 45Gy/30# BD + conc Cispl/Etop x4 • (B) 70Gy/35# OD + conc Cispl/Etop x 4 • (C) 61,2Gy/34#. 1,8Gy OD for 16 days then CONCOMITANT BOOST 1,8Gy BD x 9days T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
• IMRT: no significant diff LC or OS compared to 3D RT. Consider if v20> 30% or FEV1 <1. Less oesophagitis + PEG placement with IMRT • Post Chemo Volumes. Include pre chemo involved nodes. BUT NOT elective nodal xrt. • Auperin Meta-analysis of PCI (NEJM 1999) – PCI for LC SCLC if CR after chemo – Improved OS at 3 years by 5% – Incidence of brain mets decrease from 58 – 33% at 3years T: +27(0)51 401 9111 | info@ufs.ac.za | www.ufs.ac.za
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