Sublobar Resection and Intraoperative Brachytherapy for Lung Cancer: ACOSOG Update Rodney J. Landreneau, MD Professor of Surgery The Heart Lung and Esophageal

Sublobar Resection and Intraoperative Sublobar Resection and Intraoperative Brachytherapy for Lung Cancer:Brachytherapy for Lung Cancer:

ACOSOG UpdateACOSOG Update

Rodney J. Landreneau, MDRodney J. Landreneau, MDProfessor of SurgeryProfessor of Surgery

The Heart Lung and Esophageal Surgery The Heart Lung and Esophageal Surgery InstituteInstitute

University of Pittsburgh Medical CenterUniversity of Pittsburgh Medical Center

Surgical Treatment of Lung CancerRadiofrequency Ablation to VATS Lobectomy

November 13-14, 2008Pittsburgh, Pennsylvania

Surgical Resection of the LungSurgical Resection of the Lung

Standard of Care for Peripheral Standard of Care for Peripheral NodulesNodules

1940’s Pneumonectomy

1960’s Lobectomy

1990’s ? Segmentectomy/Wedge (and adjuvant local/systemic Rx)

● Non-small cell lung carcinoma (NSCLC) Non-small cell lung carcinoma (NSCLC) identified in patients with impaired identified in patients with impaired cardiopulmonary reserve creates important cardiopulmonary reserve creates important therapeutic challenges. therapeutic challenges.

● Sublobar pulmonary resection is often Sublobar pulmonary resection is often utilized in these patients, however, local utilized in these patients, however, local recurrence is high (15-25%).recurrence is high (15-25%).

BackgroundBackground

How Can Therapy to Customized for Patients How Can Therapy to Customized for Patients with Poor Cardiopulmonary Reserve?with Poor Cardiopulmonary Reserve?

● Primary external beam radiation therapyPrimary external beam radiation therapy- ? survival? survival

● ChemotherapyChemotherapy- no defined role as primary therapyno defined role as primary therapy

● Radiofrequency AblationRadiofrequency Ablation- ? survival? survival

● Sublobar resectionSublobar resection● Sublobar resection with adjuvant radiation therapySublobar resection with adjuvant radiation therapy

● Postoperative (postop) external Postoperative (postop) external radiotherapy following sublobar resection is radiotherapy following sublobar resection is time consuming and can result in additional time consuming and can result in additional loss of pulmonary function.loss of pulmonary function.

● We review our experience using intra-We review our experience using intra-operative operative 125125I lodine brachytherapy following I lodine brachytherapy following sublobar resection of stage I NSCLC in sublobar resection of stage I NSCLC in patients with impaired cardiopulmonary patients with impaired cardiopulmonary reserve.reserve.

BackgroundBackground

● From 1/1989 to 7/1994, 102 patients (mean age From 1/1989 to 7/1994, 102 patients (mean age 69.5 years) with pathologic stage I NSCLC and 69.5 years) with pathologic stage I NSCLC and poor cardiopulmonary reserve (mean % predicated poor cardiopulmonary reserve (mean % predicated FEV 1 preop = 65%) underwent sublobar resection FEV 1 preop = 65%) underwent sublobar resection as primary therapy.as primary therapy.

● We have since (1/1997 to 6/2002) introduced We have since (1/1997 to 6/2002) introduced adjunctive intraoperative brachytherapy with adjunctive intraoperative brachytherapy with 125125I to I to sublobar resection among 96 stage I patients with sublobar resection among 96 stage I patients with similar cardiopulmonary compromise (mean % similar cardiopulmonary compromise (mean % predicted FEV1 preop = 53%).predicted FEV1 preop = 53%).

MethodsMethods

● After resection, a vicryl™ implant containing After resection, a vicryl™ implant containing 125125I I seeds, sewn at 1cm² intervals, was placed over the seeds, sewn at 1cm² intervals, was placed over the resection staple line covering a 2cm lateral margin. resection staple line covering a 2cm lateral margin. A local radiation does of 10,000 cGy was delivered.A local radiation does of 10,000 cGy was delivered.

● No post-op patient isolation was required per No post-op patient isolation was required per national radiation safety guidelinesnational radiation safety guidelines

● Mortality and morbidity, local recurrence and Mortality and morbidity, local recurrence and disease free survival have been compared.disease free survival have been compared.

MethodsMethods

Sublobar Resection

(n=102)

Sublobar Resection

With Brachy (n=96)

Local Recurrence 19 (18.6%) 1 (1%) p=.0001

Hospital Mortality 0 (0%) 3 (3%) p=ns

Hospital Stay 7 days 8 days p=ns

Survival %

1, 2, 3 and 4 year 93, 73, 68, 60% 96, 82, 70, 67% p=ns

Systemic Recurrence 29 (28.4) 22 (23%) p=ns

Pre-op FEV 1%predicted

65% 53% p=ns

● The FEV 1 did not change postoperatively in the sublobar The FEV 1 did not change postoperatively in the sublobar resection with brachytherapy group in the interval of follow-upresection with brachytherapy group in the interval of follow-up

ResultsResults

● Local recurrence of NSCLC following Local recurrence of NSCLC following sublobar resection with intra-operative sublobar resection with intra-operative 125125Ibrachytherapy (1%) appears to be less Ibrachytherapy (1%) appears to be less than following sublobar resection alone than following sublobar resection alone (18.6%).(18.6%).

● This safe, pulmonary function preserving, This safe, pulmonary function preserving, and practical intra-operative brachytherapy and practical intra-operative brachytherapy method may be considered when sublobar method may be considered when sublobar resection is utilized as compromise therapy resection is utilized as compromise therapy of stage I NSCLC.of stage I NSCLC.

ConclusionsConclusions

ACOSOG Z4032ACOSOG Z4032

Sublobar Resection vs. Sublobar Resection vs. Sublobar Resection with Sublobar Resection with

Intraoperative Brachytherapy for Intraoperative Brachytherapy for High Risk Stage IA Non Small Cell High Risk Stage IA Non Small Cell

Lung Cancer PatientsLung Cancer Patients

High riskpatients withsuspected or

proven NSCLC

Pre-Registration and

Randomizationto Z4032

HistologicalconfirmationNSCLC and

confirmationN2/N3

negative lymphnodes

(if necessary)**

R

E

G

I

S

T

R

A

T

I

O

N

ARM 1:SublobarResection

(SR)

ARM 2:Sublobar

Resection +Brachytherapy

(SRB)

F

O

L

L

O

W

U

P

SCHEMASCHEMA

Patient SelectionPatient Selection

Eligibility CriteriaEligibility Criteria

Part I: Pre-Operative Criteria (Pre-Registration/Randomization):

● Patients must have a suspicious lung nodule for clinical Stage I NSCLC.

● Patient must have a mass ≤ 3cm maximum diameter by CT size estimate: Clinical stage Ia or selected Ib (i.e., with

visceral pleural involvement.

● Patient must have a CT scan of the chest with upper abdomen within 60 days prior to date of pre-registration.



● Patient must meet at least one major criteria or meet a minimum of two minor criteria as described below:

Major Criteria

- FEV1 ≤ 50% predicted- DLCO ≤ 50% predicted

Minor Criteria

- Age ≥ 75- FEV1 51-60% predicated- DLCO 51-60% predicated- Pulmonary hypertension (defined as a pulmonary artery

systolic pressure greater than 40mmHg) as estimated by echocardiography or right heart catheterization





Minor Criteria

- Poor left ventricular function (defined as an ejection fraction of 40% or less)

- Resting or Exercise Arterial pO2 ≤55mm Hg or SpO2 ≤88%- pCO2 45mm Hg- Modified Medical Research Council (MMRC) Dyspnea

Scale ≥3


Modified Medical Research Council Scale

Grade Description

0 No breathlessness except with strenuous exercise

1 Breathlessness when hurrying on the level or walking up a slight hill

2 Walks slower than people of the same age on the level because of breathlessness or has to stop for breath when walking at own pace on the level

3 Stops for breath after walking about 100 yards or a few minutes on the level

4 Too breathless to leave the house or breathless when dressing or undressing



● Patient must not have had previous intra-thoracic radiation therapy.

● Women of child-bearing potential must have negative serum or urine pregnancy test.

● No prior invasive malignancy, unless disease-free for ≥ 5 years prior to pre-registration (Exceptions: non-melanoma skin cancer, in-situ cancers).


Part II: Intra-Operative Criteria (Registration):

● Patient must have biopsy-proven NSCLC.

● Patient must have all suspicious mediastinal lymph (>1 cm short-axis dimension on CT scan or positive on PET scan) assessed by one of the following methods to confirm

negative involvement with NSCLC (Mediastinoscopy, endo-esophageal ultrasound guided needle aspiration, CT-

guided, video-assisted thoracoscopic or open lymph node biopsy).

ACOSOG Z4032ACOSOG Z4032

Accrual SummaryAccrual Summary

● 174 Patients Accrued Nationally

● Accrual Goal is 226 Patients

● Estimated Study Closure - November 2009

Thank YouThank YouThank You

Documents

Sublobar Resection and Intraoperative Brachytherapy for Lung Cancer: ACOSOG Update Rodney J. Landreneau, MD Professor of Surgery The Heart Lung and Esophageal