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Case study

Dr.Divyesh Kumar

Assistant Professor

Department of Radiotherapy & Oncology

Regional Cancer Centre, Chandīgarh,India

ESMO PRECEPTORSHIP PROGRAM

Case Study� 56 year old female presented to our OPD with history of cough and

weight loss with loss of appetite since 3 months. She is a non-smoker, with no h/o Koch's disease nor any other family members having similar symptoms.

� O/E-she is average built, afebrile with no pallor,lymphadenopathy,cyanosis,clubbing,edema.

� CXR done showed 1.5 x 2.0 cm pulmonary nodule in the left upper lobe, further CECT done showed a left upper pulmonary nodule almost of the same size as was visible on CXR (Fig-1).

ESMO PRECEPTORSHIP PROGRAM

� PETCT done showed a left upper pulmonary nodule with a maximum SUV of 22.7,suspicious for pulmonary lung malignancy with no evidence of disease elsewhere.

� A CT-guided needle biopsy was obtained , pathologic review of the biopsy specimen was consistent with poorly differentiated non-small cell lung cancer (NSCLC).

ESMO PRECEPTORSHIP PROGRAM

�Diagnosis of carcinoma left lung with stage (T1N0M0) was made.

� Patient was given option of SURGERY/SBRT

ESMO PRECEPTORSHIP PROGRAM

� What is SBRT?

� Why was the option given?

� How did we do it?

SBRT definition

Stereotactic body radiation therapy (SBRT) / SABR is a novel

treatment modality in radiation oncology that delivers a very high dose of radiation to the tumor target with high precision using single or a small number of fractions

(typically 5 or less).

Critical Reviews in Oncology/ Hematology (2012)

as approved by the Common Procedural Terminology (CPT®) Editorial Panel

SBRT Requires-

• 1.Higher confidence in tumor targeting.

• 2.Reliable mechanisms for generating focused, sharply delineated dose distributions.

• 3.Reliable accurate patient positioning accounting for target motion related to time dependent organ movement.

Patient selection criteria for SBRT in early stage

NSCLC

�Medically inoperable – PFT ( FEV1 or DLCO < 40%), DM/CAD, cerebral disease, Pul. HTN

� Patient choice to avoid surgery

� PS 0-2

� Stage T1-2, N0 following PET-CT

�Max tumour size < 5cm

�Not adjacent to major vessels, heart, esophagus etc

� Able to lie flat for at least one hour

Inference-

� two-year local control was 95%.

� median overall survival was 33 months

� Eight of the 70 patients developed a grade 3- 4toxicityincluding pneumonia, pleural effusion, apnoea, skin reactionand decline in pulmonary function tests.

� Six patients died as a result of toxicity.

LungProspective studies of SBRT in Primary Lung

Cancer

Institution N SBRT dose and

Fractionation

Results

Indiana

University

47 60Gy/3# Phase I study; MTD not

reached for T1 lesions;

MTD 66 Gy for T2 lesions

Indiana

University

70 60 – 66Gy /3# 1-y local control 98%

Aarhus

University

40 45 Gy/3 # 2-y local control 85%

Kyoto University 45 48Gy / 4# 2-y local control 95%

Air Force General

hospital, Beijing

43 50Gy/ 10 # 1-y local control 95%

University of

Marburg

33 30 Gy/1 # 1-y local control 94%

Inference-

� 3-year LC of 97.6%,

� lobar control of 90.6%,

� LRC of 87.2%,

� 22.1% rate of distant recurrence7, consistent with other series.

The evidence for SBRT: Lung

cancer

What is the ideal SBRT dose? Excellent local control is seenwith 60 Gy in 3 fractions as perRTOG 0236, although otherregimens (48 Gy/4, 50 Gy/5, and60 Gy/5) have similar outcomeswithout requiring as high of abiologically equivalent dose(BED).

Ongoing studies

• RTOG-0813: a multi centre phase II study evaluating dose escalation in patients with centrally located tumors of less than 5 cm (T1-2N0M0) in order to determine the maximum dose and toxicity profile of SBRT delivered in 5 fractions. Other outcome measures include local control rates, overall survival, and progression-free survival.

•• RTOG-0915:a phase II study of medically

inoperable patients with stage I NSCLC. Patients are randomized to receive 34 Gy in 1 fraction or 48 Gy in 4 fractions.

2009

LC (5 yrs) � 92% ( IA) 73% ( IB)

Pulmonary complications > Gr 2 seen in 1 patient (1.1%)

� Randomized comparison of Surgery vs SABR for

operable patients ( stage 1)

ROSEL STUDY (Vumc & Dutch study group)

- lobectomy Vs SBRTACOSOG Z4099/RTOG 1021

- Wedge vs SABR

*STARS Trial � Lobectomy vs SABR

*MAYO Trial � sublobar Sx Vs SABR

*ACCURAY Trial

A Matched Pair Analysis of Stage I Non-Small Cell Lung Cancer Treated With Lobectomy, Stereotactic Radiation Therapy

(SBRT), or Wedge Resection

• 286 pts: L (89), W (69), or SBRT (128): 39 pts in each of 3 well-matched groups. 90

day mortality “0” in all groupsASTRO 2013, Int J of Rad Onc Bio Phy Vol. 87 (2), S10

Retrospective data: SBRT for Operable pts?

* Onishi, Int J Radiat Oncol Biol Phys 2011; 81: 1352-58; ** Lagerwaard, Int J Radiat Oncol Biol Phys 2012; 83: 348-353;

Study *Japan data (87 pts) **Netherlands (177 pts)

Age 74 yrs 76 yrs

T1, T2 65, 22 pts (2.5 cm) 106, 71 pts (2.6 cm)

RT dose 42-72.5 Gy in 3-10 # 60 Gy in 3-8 #

Median FU 55 months 31.5 mo

5 yr OS 69.5% 51.3% (median: 61.5 mo)

5 yr LC (T1, T2) 92%, 73% 93% @ 3 yrs

Grade 3 RP 1.1% 2%

30 day mortality 0% 0%

PET scan for staging, LN staging limited, Biopsy done in only 33%, Prognostic factors:

female

Prospective studies: SBRT for Operable pts

*Nagata, ASTRO 2012, **Timmerman, ASCO 2013

2013

45 reports ( 2006 - 2012) containing 3771 patients, stage 1 NSCLCSABR � 2yr LC 91% , OS 70% ( 95% CI : 67-72)Surgery � 68% (95% CI: 66–70)

No survival or local PFS difference with different radiotherapy technologies used for SABR.

� patients with early stage NSCLC treated with SBRT had similar DFS, CSS, LC and DC as patients treated with surgery but worse 3-year OS ( ?? Better patient profile)

� Phase 3 randomised direct comparison � highly recommended

* Radiation pneumonitis-

1. total lung V5 of >37% and c/L lung V5 > 26%

2. higher V40 -- > faster RP

3. MLD

** Chest wall toxicity-

1. Chest wall dosimetry : V30 < 30 mm3

V60 < 3 mm3

2. Tumors > 1 - 2 cm from the chest wall

and 5 cm from the posterior skin -- > low risk

PREDICTORS FOR TOXICITY

*Dutch study

*Michael strauder, Green journal 2012

** Kevin I Stephans, Red Journal 2012

• Patient opted for SBRT.

• SBRT was planned with a dose of 48 Gy in 4 #,12 Gy/#.

ESMO PRECEPTORSHIP PROGRAM

� Pre-treatment CECT images with fudicial markers was obtained (Fig-2) .

� Planning was subsequently done.(Fig3).

ESMO PRECEPTORSHIP PROGRAM

� Treatment Planning Process-The patient was treated with multiple non-iso-centric, non-coplanar beams at the tumor. This delivered a large dose of radiation to a small field while sparing surrounding normal tissues and other critical structures. Prior to the procedure, the patient had permanent fiducial markers placed near the treatment site , then was immobilized in an Alpha cradle. CT were performed ,on each of the axial slices the gross tumor volume (GTV) was outlined to digitally reconstruct a 3-dimensional planning tumor volume (PTV) that measured 13.85 cc. The PTV had a 5-mm margin with respect to the GTV.

ESMO PRECEPTORSHIP PROGRAM

� The treatments were delivered on 4 consecutive days. The patient tolerated the treatment well, experiencing no ill effects or changes in her pulmonary status during the therapy.

� Post treatment radiological investigations done (CECT & PET CT) showed no e/o disease. Patient has been kept on close follow ups.

ss

• Follow-up recommendations based on the current evidence1. serial computed tomography (CT) imaging at 3–6 months post treatment for the initial year, then every 6–12months for an additional 3 years, and annually thereafter.

2.With suspicion of progressive disease positron emission tomography.

3.Biopsy and/or surgical or nonsurgical salvage therapy can be considered if safe and when investigations are non reassuring.

SABR and quality of life (QOL)

Laagerwaard et al 2012 J Thor Oncol, 7, (7); 1148-1194

Quality of life after SABR (EORTC QLQ C30)

Change in global QOL score

Frank J. Lagerwaard, Neil K. Aaronson, Chad M. Gundy, Cornelis J.A. Haasbeek, Ben J. Slotman and Suresh

Senan

� SABR is a highly effective treatment for stage I NSCLC, with limited toxicity.

� In contrast to surgery, SABR does not lead to significant worsening of QOL in the

first year after treatment

2012

� Quality of life was maintained, and emotional functioning improved significantly

after SBRT for stage I NSCLC, while

� survival was acceptable, local tumor control was high, and toxicity was low.

2010Noelle C Van der Voort et al.

CONCLUSION

1. SBRT is an effective treatment option for early-stage (T1/T2N0) NSCLC of < 5 cm.

2. Patients who are not surgical candidates constitute the principal study population.However, SBRT is a treatment option for patients who are unwilling to undergo surgery.

3. Patients with peripheral tumors and those with central tumors can be treated with SBRT, although with different dose fractionation schedules.

4. Patients with multiple lesions or previous radiation therapy should be evaluated to receive SBRT.

5. Limited lung function and advanced age are not contraindications to SBRT.

6. The early termination of randomized studies comparing SBRT with surgery in operable patients demonstrates the difficulty in conducting phase III studies on this topic. However, evidence from a pooled analysis of two such studies shows that, in operable patients, SBRT is at least equivalent to surgery in terms of local control and survival, and has reduced toxicity.