Multidisciplinary treatment of thoracic malignancies

Jussuf T. Kaifi, M.D., Ph.D., F.A.C.S.

Chief, Division for Cardiothoracic Surgery

Co-Director, Clinical Trials Office

Ellis Fischel Cancer Center

Medical Oncologist

Pulmonologist

Radiologist

RadiationOncologist

Surgical

Oncology

Multidisciplinary Care in Thoracic Diseases

PATIENT

Nutritionist

Respiratory therapists

Cancer RegistrarsNurse Navigators

Patient Navigators

• HIGHEST VALUE

• ENROLL IN CLINICAL TRIALS

Value in (multidisciplinary) Healthcare

‘The State of Value in U.S. Health Care’, University of Utah, Nov. 2017

Smoking in Missouri

• 7th highest smoking rate in the US (22.1%)

• Average pack of cigarrettes: $5.25

• 30 pack years:

– 219,000 cigarettes

– $57,488

Lung cancer

• USA:

– >220,000 new lung cancer cases/year

– 160,000 deaths/year

– 440 deaths/day

• Worldwide: Never-smoker: 20% men, >50% women

• Overall 5-year survival: 18%

Boeing 747: 416 passengers

Parkin et al. Global cancer statistics, 2002., CA Cancer J Clin. 2005

Lung cancer in Missouri:

• New Lung Cancer patients in 2018: 5,620

• Deaths due to Lung Cancer in 2017: 4,030

• Death rate 56/100,000

• Economic impact: $5.4 billion over next 4 years

Cancer Facts and Figures 2017, American Cancer Society

Operable patient: Surgery

Lymph node status:

N0 N1

NSCLC: Stage I/II

Tumor size

NSCLC Survival Stage I/II: 30-60%

Silvestri GA, Gould MK et al, Chest 2007, 132(3) 179S

Low-dose CT screening improves survival

53,454 high-risk patients

Randomized:

3x/year low-dose CT vs. CXR

(Effective radiation doses:

chest x-ray: 0.1 mSv; LDCT: 2 mSv; traditional chest CT: 7 mSv)

low-dose CT:

20% reduction in lung cancer-related mortality

Lung cancer screening eligibility

- 55-80 years old

- ≥30py smoking history

- Current smoker or quit within past 15 years

- Ellis Fischel Cancer Center:

- >1500 screened since 2016

Screening with LDCT: - 1 out of 4 has lung nodule

- False-positive rate >95%

Benign

(necrotizing granuloma/

histoplasmosis)

Lung cancer

(NSCLC stage IA)

Case• 72 yo female

• 50 py smoking history

• Screening low-dose CT:

right upper lobe lung mass

• PET/CT: FDG-avid, no mediastinal

lymphadenopathy

• Good PFTs (FEV1: 2l, DLCO 85%)

• Robotic wedge (frozen: cancer), right upper

lobectomy with mediastinal lymphadenectomy

• Pathology: stage IA NSCLC (SCC)

Lung Lobectomy

• Indications:

– Stage I-II

– Selected stage IIIA (single-level N2)

– Selected stage IV (oligometastatic to lung, brain or adrenal)

• 30 day mortality: 2.2%

– Society for Thoracic Surgery (STS) Database 2010:

n=18,800 from 111 centers in the US

Minimally invasive (VATS) Lobectomy

• Standard lobectomy

• No rib spreading

• Small incisions

• Safe, oncologically equivalent

• Decreased pain, faster recovery

Hansen et al., Surg Endosc 2011

Slow adoption of VATS lobectomy in the US

AHRQ HCUPnet database

Open

Open

VATS16 years

Robotic lung surgery:

Same advantages as VATS,

better vision and instrumentation

Robotic lobectomy trend 2009-17

Premier multihospital database

Open

VATS

Robotic

%

2009 2017

Multicenter registry study of long-term

oncologic results of robotic lobectomy

• 2002-2010, 3 centers, n=325

• >95% stage I

• Median operative time: 206 minutes

• Conversion rate: 8%

• Mortality rate: 0.3%

• Major complications (BPF, PE, ARI, hemorrhage, MI): 3.7%

• Median chest tube duration: 3 days (1-23)

• Median LOS: 5 days (2-28) Park BJ, et al. Robotic lobectomy for

NSCLC: long term oncologic results

JTCVS 2012

Robotic thoracic surgery at Mizzou

• 05/2016 - 04/2018: 117 cases

• 54 lung lobectomies:

– No 90-day mortality, 7 conversions (13%), 1 re-operation (hemothorax),

no major complications (BPF, PE, ARI, MI),

median LOS: 3 days (range 1-14), 5 (9%) readmissions

• 63 others (wedges, thymectomies, esophagectomies,

mediastinal/pleural tumors, etc.):

– No 90-day mortality/conversions/major complications

– 44 lung wedges, median LOS: 2 days (range 1-8), 2 (5%) readmissions

Case• 79yo male, 80py

• Low-dose screening CT: RLL lung mass

• Biopsy: TTF-1+ adenocarcinoma

• Clinical stage IA

• Medically inoperable: FEV1 0.6l, home oxygen, immobility

• Treatment:

Stereotactic body radiation

SBRT• Stage IA lung cancer

• 55 Gy in 5 fractions, 30 minutes daily over 5 days

• Meticulous tissue sparing (esophagus, chest wall)

• Challenges: central tumors with proximity to airway, major

vessels, spinal cord; local recurrences

Heinzerling, The Cancer Journal 2011

SBRT: NCCN guidelines

• Medically inoperable

• No lymph node metastases (cN0)

• Tumor size <5cm

Higher risk patients: Sublobar resections

(wedge resection/segmentectomy)

McKenna RJ, Ann Thorac Surg 2008

Wedge resection Segmentectomy Lobectomy

Local recurrence 16-31% 2-23% 1-11%

5-year survival 26-69% 43-93% 67-90%

Ablative techniques (RFA, microwave)• Percutaneous, CT-guided ablation:

– Microwave superior: lung has low electrical conductivity & poor thermal

conduction, allowing larger ablation zone than RFA

• Peripheral lesions <3cm (clinical stage I)

• Contraindication: adjacent to major bronchovascular

structures, diaphragm or esophagus; severe emphysema

• Few clinical studies, can be repeated, less collateral damage,

can be integrated in multimodal treatment

2 years post-ablationRUL NSCLC Microwave ablation

NSCLC Survival by Stage

Silvestri GA, Gould MK et al, Chest 2007, 132(3) 179S

N2 N3

Stage III: definitive chemoradiation

mN2L1 mN2L2+ cN2L1 cN2L2+

5-yr survival 34% 11% 8% 3%

Andre F et al. J Clin Oncol 2000;18:2981-2989.

702 pts, N2 disease

(stage IIIA)

Resection with curative

intent

N2: ≥ Stage IIIA

Single level N2: better survival after surgery

Stage IIIA (T1-3, single level N2)

resectable

Neoadjuvant

chemo(radio)therapy

If ypN2: adjuvant mediastinal radiation

Stable disease or remission:

Surgery

Multimodal treatment for stage IIIA (single level N2)

NSCLC Survival by Stage

Silvestri GA, Gould MK et al, Chest 2007, 132(3) 179S

Stage IV:

Median survival

8-10 months

Palliative

chemotherapy

Oligometastatic NSCLC

• Synchronous or metachronous

• Sites: lung, brain, and adrenal gland

• Multimodal management: radiation, surgery, chemotherapy

• Brain: SBRT / surgery followed by SBRT/WBRT; prospective single-arm

phase II trial: 3-year OS 18%

• Adrenals: adrenalectomy / SBRT (5 year survival: 34% vs. 0%)

• Phase II RCT: local consolidative therapy (RT/surgery) to oligometastatic

lesions (≤3), not progressing on systemic treatment:

median PFS 11.9 vs. 3.9 months

De Ruysscher et al; J Thorac Oncol. 2012

Raz et al; Ann Thorac Surg 2011

Gomez et al; Lancet Oncol 2016

Targeted treatment to improve

survival of early stage lung cancer

Resected NSCLC stage I-III:

• 5-year survival: 30-60%

• Adjuvant chemotherapy (4 cycles; platinum-based double):

+5% survival benefit / 5 years

Hirsch et al., Lancet 2017The IALT Collaborative Group, NEJM 2004

JBR.10 Trial Investigators. NEJM 2005

Targeted therapies: NSCLC

• EGFR overexpression/mutation (IHC, mutational analysis):

– 30% never-smoking females of East Asian origin, 15% in Caucasians (adenocarcinomas)

– Erlotinib: PFS benefit: 10.4 vs. 5.2 months (median)

• EML4/ALK fusion (FISH):

– 5% NSCLC/adenocarcinomas

– Crizotinib: PFS benefit for untreated stage IV: 10.9 vs. 7.0 months (median)

• PD-L1 overexpression (IHC):

– 30% of NSCLC PD-L1+

– Immune checkpoint inhibitors, also for SCC

– Pembrolizumab: PFS benefit for stage IV: 10.3 vs. 9.0 months (median); response rates 45% vs. 28%

Shepherd et al, NEJM 2005

Garon et al, NEJM 2015

Herbst et al, NEJM 2016

Clinical Trials Office, EFCC

• Ken Baker, RN (Manager)

• Angela Waller, RN

• Sue Prenger, RN

• Elizabeth Porting-Jackson

• Marta Fuemmeler

• Sherezad Mistry

Co-Directors:

• Puja Nistala, MD

• Jussuf T. Kaifi, MD

– ALCHEMIST group

– NCI-sponsored National Clinical Trials Network (NCTN)

initiative

– Addresses the need to refine therapy for early-stage NSCLC

observation

observation

kaifij@health.missouri.edu