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Kidney Cancer and Radiation

Dr P S Bhattacharyya. MD● Radiation Oncologist

● Mahatma Gandhi Cancer Hospital



Kidney Anatomy:



EPIDEMIOLOGY

Equal racial distribution2:1 male to female distribution

Occurs in 5th to 7th decade of life

Tobacco greatest risk factorObesity may be a risk factor

Most cases sporadic, yet also occurs withVon Hippel-Lindau disease (VHL) [45%],and less commonly with tuberoussclerosis, and in rare familial distributions



INCIDENCE

● Incidence – There are approximately 30,000 new cases per year and

12,000 cancer related deaths

– Incidence is rising 6.1 to 9.3 per 100,000 over 20 years

– Mortality rate has not decreased even with greater

detection of small tumors

Lead time bias

Short follow up

Less aggressive? – 25% of tumors present with advanced disease



BHD=Birt-Hogg-Dubé; FH=fumarate hydratase; VHL=von Hippel-Lindau.

Modified from Linehan WM et al. J Urol . 2003;170:2163-2172.

RCC is not one disease

Clear cell

75%

Type

Incidence (%)

Associatedmutations

VHL

Papillary type 1

5%

c-Met

Papillary type 2

10%

FH

Chromophobe

5%

BHD

Oncocytoma

5%

BHD

*2004 WHO lists over 50 different types of kidney cancer

(Sarcomatoid variant can occur with any subtype)

Undifferentiated type and Collecting duct carcinoma

constitute the other 2 types listed in AJCC classification



Spread

Renal capsule to involve the perinephricfat and Gerota's fascia.

Renal vein-21% or Vena cava-4%

LN metastases 9% to 27% and mostoften involve the renal hilar, para-aortic,and paracaval lymph nodes.



PROGNOSIS

STAGESTAGE 5 YR5 YR 10 YR10 YR

I (T1)I (T1) 90%90% 80%80%

II (T2)II (T2) 80%80% 70%70%

III (N1)III (N1) 50%50% 35%35%

IV (T4)N2IV (T4)N2 10%10% 3%3%



FOLLOW-UP

– Traditionally, most patients with sporadic RCC are followed every 6months or yearly with a history and physical examination (H&P), liver

function studies, serum chemistry (including alkaline phosphatase),

CXR, and abdominal cross-sectional imaging.

T1: H&P, serum chemistry, and CXR yearly for 5 years

T2: H&P, serum chemistry, and CXR every 6 months;

abdominal CT scan at 2 and 5 years for 5 years

T3: H&P, serum chemistry, and CXR at 3 months, then every

6 months; abdominal CT scan at 2 and 5 years



CLINICAL PRESENTATION

A QUARTER PRESENT WITH ADVANCED

DISEASE, LOCALLY ADVANCED OR

METASTATIC

A THIRD OF PATIENTS POST SURGERY FOR

LOCALISED DISEASE WILL RELAPSE

WITH METASTATIC DISEASE THE MEDIAN

SURVIVAL IS 13 MONTHS



CLINICAL PRESENTATION

THE CLASSIC TRIAD <10 %

INCIDENTAL DETECTION ALMOST 7%

SYSTEMIC SYNDROMES – ANAEMIA, FATIGUE, CACHEXIA, WEIGHT LOSS,

HYPERCALCEMIA, HEPATIC DYSFUNCTION

RARE SYNDROMES – ERYTHROCYTOSIS, ENtEROPATHY, NEUROPATHY,

AMYLOIDOSIS



CLINICAL PRESENTATION 45% localized disease

25% regional disease

30% distant metastases Lung 75%, Soft tissue 36%Bone 20%, Liver 18%

1% to 3% have solitary lesions

50 % eventually develop

metastatic disease



CLINICAL STAGING

Chest X-ray or Chest CT

CT/MRI scan of abdomen or pelvis(Johnson et al. 1987;

Ultrasound with color-flow Doppler(McClennan 1991).

Bone scan with plan films (for elevated alkaline

phosphatase or bone pain).

Laboratory: CBC, LFT's, alkaline phosphotase,

BUN, creatinine.FDG-PET or PET/CT (optional)(Martinez et al. 2007; Ramdave et



RADIATION TRIALS

PREOPERATIVE RT

POST OPERATIVE RT



PREOPERATIVE RT

EVIDENCE GAINED FROM LAB

REDUCES TUMOR SEEDIND DURING SX(99)

TUMOR SHRINKAGE , DECRESED TUMOR

VIABILITY AND REDUCED DISTANT METS(115)

PROSPECTIVE PREOP RT TRIALS(35,113).

RT+ SX vs SX- 5 yrs OS -47% vs 63%(61)



POST OPERATIVE RT

Beneficial in early retrospective trials(9,110)

New Castel, UK Randomised trial-Inferior

survival in SX+RT arm(39)

Copenhagen Renal cancer Study Group-no difference in local relapse(69)



PATIENTS GROUPS TO BENEFIT

FROM PORT 172 patients at Memorial Sloan-Kettering Cancer Center T1/T2 RCC

treated by radical nephrectomy demonstrated an overall local failure

rate of only 5%

Patients with lymph node metastases or positive margins had a

significantly higher local failure rate of 21%Kao et al. (62) reported that, in a retrospective series, 12 patients

with high-risk, locally advanced tumors with perinephric invasion or

surgically positive margins had a 100% local control rate if treated

adjuvantly with postoperative irradiation

T3 tumors had a statistically significant lower local failure rate (10%)

with PORT, vs (37%) nephrectomy alone (124)



PATIENTS GROUPS TO BENEFIT

FROM PORT

Based on this collection of both prospective and

retrospective data,(62,79,124).

indications for RT should be considered:

(a) unresectable nonmetastatic tumors and

(b) incomplete resection with gross or

microscopically positive margins, LN+ .(Grade c)

(c)Neoadjuvant radiation therapy can be

considered in unresectable locally advanced

renal cell carcinoma (Grade C)



THANK YOU



Sorafenib (Nexavar ®)• Small-molecule receptor TKI1

• Inhibits VEGFR-2, VEGFR-3, FLT-3, PDGFR, c-KIT, Raf kinases1

• Formulation: 200 mg tablets2

• Dosing: 2 tablets bid continuous (1 hr ac or 2 hrs pc)2

• FDA approved December 20, 2005 for advanced RCC3

1. Wilhelm SM et al. Cancer Res. 2004;10:7099-7109.

2. Nexavar [package insert]. West Haven, CT: Bayer Pharmaceutical Corporation and Emeryville, CA:

Onyx Pharmaceuticals, Inc.; 2005.3. Food and Drug Administration. FDA approves new treatment for advanced kidney cancer.

Available at: www.fda.gov/bbs/topics/NEWS/2005/NEW01282.html. Accessed January 24, 2006.

NH

NH

O

OO

N

CI

CF3

NH

CH3



Median PFS from randomization

Sorafenib=24 weeksPlacebo=6 weeks

P =.0087

Sorafenib for mRCC: Phase II (RDT)

Progression-Free Survival

Time From Randomization (days)

P r o p o r t i o n o f

P a t i e n t s

P r o g r e s s i o

n - F r e e

1.00

0.75

0.50

0.25

0

12-week

period

84 0 100 200 300 400 500

Ratain MJ et al. Presented at: ASCO; May 13-17, 2005; Orlando FL.

Sorafenib (n=33)

Placebo (n=32)

Censored



Sorafenib for mRCC:

Overall Survival* (TARGET)

OS Median (months)

Sorafenib

Placebo

Not reached

14.7

Hazard ratio (S/P) 0.72P =.018

Censored observation

Placebo (n=452)

Sorafenib (n=451)

Time From Randomization (months)

P r o p o r t i o n o f

P a t i e n t s

O v e r a l l S u r v i v a l

0

0.25

0.50

0.75

1.00

0 4 10 202 6 8 12 14 16 18

*Interim analysis.

Escudier B et al. Presented at: ECCO; October 30-November 3, 2005; Paris, France.



Sunitinib (Sutent®)

• Small-molecule receptor TKI1

• Inhibits all VEGFRs, PDGFR-a, PDGFR-b, c-KIT, and FLT-31

• Formulation: 12.5 mg, 25 mg, 50 mg capsules2

• Dosing: 50 mg qd ± food(4 wks on, 2 wks off)2

• FDA approved January 26, 2006

for advanced RCC

1. Pietras K, Hanahan D. J Clin Oncol. 2005;23:939-952.

2. Sutent [package insert]. New York, NY: Pfizer Inc.; 2006.

H3C

CH3

FO

O

CH3

CH3

N

H

N

H

N

N

H

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