COMPLICATIONS OF RADIATION THERAPY FOR CHILDHOOD CANCERS - - PowerPoint PPT Presentation

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COMPLICATIONS OF RADIATION THERAPY FOR CHILDHOOD CANCERS - - PowerPoint PPT Presentation

Aug 15, 2022 38 likes •556 views

COMPLICATIONS OF RADIATION THERAPY FOR CHILDHOOD CANCERS Siddhartha Laskar Associate Professor Department of Radiation Oncology Tata Memorial Hospital, Mumbai INDIA (laskars2000@yahoo.com, www.tatamemorialcenter.com) S Laskar ICARO 2009

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COMPLICATIONS OF RADIATION THERAPY FOR CHILDHOOD CANCERS

Siddhartha Laskar

Associate Professor Department of Radiation Oncology Tata Memorial Hospital, Mumbai INDIA (laskars2000@yahoo.com, www.tatamemorialcenter.com)

S Laskar ICARO 2009

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* WHO Projection - 2005 YEAR GLOBAL DEVELOPING WORLD PERCENT. (Millions) (Millions) OF GLOBAL 1985 7.6 3.9 52% 1990 8.1 4.1 51% 2000 10.1 5.4 53% 2020* 20.0 14.0 70%

CANCER BURDEN CANCER BURDEN CANCER BURDEN

NEW CASES OF CANCER “Paediatric Malignancies account for 3-5% of the burden”

S Laskar ICARO 2009

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AVERAGE ANNUAL INCIDENCE OF CHILDHOOD CANCERS

IARC 2005

S Laskar ICARO 2009

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RELATIVE FREQUENCIES OF MAJOR TUMOUR TYPES

IARC 2005

S Laskar ICARO 2009

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ROLE OF RADIOTHERAPY IN CHILDHOOD CANCERS

Hodgkin’s Lymphoma Early Stage Advanced Stage > 90% Poor Prognostic Group Nasopharyngeal Carcinoma 100% CNS Tumors > 90% Ewings Sarcoma/ PNET Definitive Post Operative 40% 30-40% Rhabdomyosarcoma IRS Gr III, Unfav. Histology NR- Soft Tissue Sarcoma > 80% Wilms Tumor Stage III FH, All UH Retinoblastoma Non Amenable to Focal Th. Vitreous Seeding Leukemia (CNS Prophylaxis) Depends upon type of CTh Neuroblastoma Residual, Unfavourable

S Laskar ICARO 2009

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5 YEAR SURVIVAL AT St JUDE CHILDRENS HOSPITAL

Courtesy: Dr Raul Riberio S Laskar ICARO 2009

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UNITED STATES DATA 1 in 640 persons between the ages of 20 and 39 years is a childhood cancer survivor (~300,000)

Courtesy: Dr Raul Riberio S Laskar ICARO 2009

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ACUTE TOXICITIES

S Laskar ICARO 2009

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Dermatitis Mucositis Enteritis Cystitis Dysphagia Xerostomia Impaired Taste Hoarseness of Voice Headache Nausea & Vomiting Hematological Radiation Dose: 50-60Gy @ 1.8-2.0Gy/ fr Potentiating Factors: Skin Condition/ Connective Tissue Disorders Prior Interventions: Surgery/ Chemotherapy Concurrent Chemotherapy Poor Nutrition & Hyegiene Poor Orodental Hyegiene Poor Skin Care Management: Optimal Sequencing with Chemo Optimal Dose/ Fractionation & RT Volume Optimal Radiotherapy Plan (skin dose) Skin Care Maintain Nutrition & Hyegiene Maintain Orodental Hyegiene

S Laskar ICARO 2009

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RADIOTHERAPY Primary: 66 – 70 Gy Neck: 50 Gy/ 25 fr CHEMOTHERAPY Neoadjuvant Concomittant Adjuvant

CARCINOMA OF NASOPHARYNX

S Laskar ICARO 2009

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IMRT CONVENTIONAL RT

DOSIMETRIC COMPARISION OF TREATMENT PLANS

S Laskar ICARO 2009

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PTV70 (70.2Gy/ 33# @ 2.12Gy/#) PTV59.4 (59.4Gy/ 33# 1.8Gy/#) PTV52.8 (52.8Gy/ 33# 1.6Gy/#)

PTV70 PTV59.4 PTV52.8

IMRT FOR CA NASOPHARYNX

S Laskar NPX IMRT 03

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IJROBP DEC 2008 S Laskar ICARO 2009

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42.8 53.4 47.2 52 32.1 55.4 41.9 57.4 10 20 30 40 50 60 Dose in Gy Spinal Cord Brain stem Contralateral Parotid Ipsilateral Parotid IMRT Conventional RT

COMPARATIVE DVH FOR CRITICAL ORGANS

Laskar, IJROBP Dec 2008

S Laskar ICARO 2009

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Laskar, IJROBP Sept 2008

S Laskar ICARO 2009

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TIME TO DEVELOPMENT OF GRADE II TOXICITY

Laskar, IJROBP Dec 2008

S Laskar ICARO 2009

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HELICAL TOMOTHERAPY

Significant Improvement in Normal Tissue Sparing

S Laskar ICARO 2009

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S Laskar ICARO 2009

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PHOTON IMRT PROTON IMRT

S Laskar ICARO 2009

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LATE TOXICITIES

S Laskar ICARO 2009

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Cardio vascular Visual Psycho social Dental Musculo skeletal Pulmo nary Gastro intestinal Genito urinary Second Tumor Endocrine Auditory Neuro cognitive Late Effects

S Laskar ICARO 2009

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CHRONIC CONDITIONS IN ADULT SURVIVORS OF CHILDHOOD CANCER

Condition Relative Risk of Grade 3 or 4 Complication as Compared to Siblings Major Joint Replacement

  • 54. 0

Congestive Heart Failure 15.1 Second malignant neoplasm 14.8 Cognitive dysfunction, severe 10.5 Coronary artery disease 10.4 Cerebrovascular Accident 9.3 Renal failure or dialysis 8.9 Hearing loss not corrected by aid 6.3 Legally blind or loss of eye 5.8 Ovarian failure 3.5

Oeffinger et al, NEJM 2006 S Laskar ICARO 2009

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CAUSE OF MORTALITY IN SURVIVORS CANCER

Recurrent Cancer Second Malignancy/ Neoplasm Cardiac Toxicity Pulmonary Disease Other Sequelae Non‐ Treatment Related Childhood Cancer Survivor Study N = 2823 57% 15% 7% 2% 4% 15% Piedmont Region, Italy N = 143 62.2% 12.6% 1.4% NA 8.4% 15.4% British Columbia, Canada N = 181 69.1% 7.7% 4.4% 2.2% 5.5% 11.1%

S Laskar ICARO 2009

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TIMELINE OF LATE EFFECTS

Paulino AC, IJROBP 2004 S Laskar ICARO 2009

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EFFECT OF RT ON MUSCULOSKELETAL DEVELOPMENT Factors Influencing Growth

  • Chronological age at treatment
  • RT volume
  • Total RT dose
  • RT dose per fraction
  • Site of treatment
  • Homogeneity of growth plate irradiated
  • Surgery
  • Chemotherapy

S Laskar ICARO 2009

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RELATIVE LOSS OF ADULT HEIGHT

  • 7.7% (13cm) with RT dose > 33Gy, Entire spine (pre-pubertal age)
  • No clinically significant loss of height with low dose RT
  • IFRT associated with clinically insignificant height loss
  • No disproportion between sitting & standing height

William KY, IJROBP 1993;28:85 Stanford

S Laskar ICARO 2009

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HEIGHT DEFICIT FROM RADIOTHERAPY

Age at treatment (yrs) Height deficit (cm) after 10Gy Height deficit (cm) after 20Gy Height deficit (cm) after 30Gy 2 2.4 4.8 7.2 4 1.8 3.5 5.3 6 1.2 2.4 3.6 8 0.8 1.5 2.3

Hogeboom et al, Med Pediar Oncol 2001 S Laskar ICARO 2009

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  • Hypoplasia of right flank

secondary to hemiabdomen RT at age 3 years for FH Wilms’ tumor

  • Dose: 36Gy in 20 fractions

S Laskar ICARO 2009

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BOWEL OBSTRUCTION

  • 131 of 1,910 children (6.9%) enrolled in NWTS-3 at median follow-up of

5.1 years

  • Etiology was bowel adhesions in 104, intussusception in 17, internal

hernia in 2

  • Risk factors: higher local tumor stage, extrarenal intravascular

involvement, en bloc resection of other organs

  • Postoperative RT not a risk factor

Ritchey ML et al, Ann Surg 1993 S Laskar ICARO 2009

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BOWEL OBSTRUCTION

  • At University of Iowa, SBO was seen in 6 of 42 children who received RT

with median follow-up of 15.1 years for Wilms’ tumor

  • 5 yrs:9.5%
  • 10 yrs:13%
  • 15 yrs:17%
  • Time from surgery to RT borderline significant (< 10 days vs. > 10 days)

Paulino et al, IJROBP 2000 S Laskar ICARO 2009

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PNEUMONITIS: NWTS-3 EXPERIENCE

  • 153 pts with Stage IV, FH received whole lung RT
  • 19 (13%) developed diffuse interstitial pneumonitis
  • 15 unknown etiology, 3 pneumocystis, 1 varicella
  • Only 4 of 15 (27%) with pneumonia of unknown etiology survived

Green DM et al, Cancer 1989

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CARDIOVASCULAR LATE EFFECTS

STANFORD (1960-1995) 2498 Pts. 754 Deaths 16% CV disease JCRT (1969-1996) 794 Pts. 124 Deaths 14% CV disease EORTC (1963-1986) 1449 Pts. 240 Deaths 7% CV disease BNLI 1043 Pts. 43 Deaths 14% CV disease

Decreasing CV deaths with improving therapy (CT & RT) Stage I & II at Stanford (CV deaths after 15yrs of treatment) 1962 - 1980: 812 pts. ------ 5.4% 1980 – 1996: 628 pts. ------ 0.8%

S Laskar ICARO 2009

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No of pts No of pts with renal failure Incidence of Renal Failure (%) 2 years 4 years 16 years Unilateral 5312 15 0.1 0.2 0.6 Bilateral

  • NWTS-1

41 7 9.8 9.8 16.6 NWTS-2 43 7 14.6 14.6 22.3 NWTS-3 181 18 6.6 8.3 12.7 NWTS-4 177 7 2.6 5.8 _

RENAL FAILURE

Ritchey ML et al, Med Pediatr Oncol, 1996 S Laskar ICARO 2009

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PREGNANCY OUTCOME

  • Increased frequency of following were seen in female patients who have

received prior flank or tumor bed RT on NWTS 1-4 Fetal malposition Premature labor Offspring with low birthweight, premature birth (< 36 weeks of gestation) and congenital anomalies

Green DM et al, JCO 2002 S Laskar ICARO 2009

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Hong et al., IJROBP 2004

3D-CRT vs. IMRT FOR EXTREMITY SARCOMAS

S Laskar ICARO 2009

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CAX 10cm SUP 3D-CRT IMRT

Hong et al., IJROBP 2004

S Laskar ICARO 2009

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Reduction of Volumes receiving 100% dose using IMRT Femur: 57% Normal Soft Tissue: 78% Normal Skin: 45% Mean Skin Dose: Decreased by 14%

Hong et al., IJROBP 2004

S Laskar ICARO 2009

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a) 3D CRT b) IMRT c) PROTONS

3D CRT vs. IMRT vs. PROTONS FOR PELVIC SARCOMA

Lee et al, IJROBP 2005 S Laskar ICARO 2009

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IJROBP 2002

S Laskar ICARO 2009

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Significant Reduction in Volume of Bony Wall of Orbit in High Dose Region

S Laskar ICARO 2009

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2002 2008

S Laskar STS CRT S Laskar ICARO 2009

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2004 2008

S Laskar STS Brachy 04 S Laskar ICARO 2009

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TYPE/ SITE RELATIVE RISK ABSOLUTE RISK /10,000 pts, Per Yr. RELATIVE RISK In 10yr survivor ABSOLUTE RISK In 10yr survivor Per 10,000 pts, Per Yr. All cancers 3.5 (3.1 – 3.8) 56.2 4.7 (3.8 – 5.7) 111.7 Leukemia 32.4 (25.5 – 40.6) 16.8 16.2 (6.5 – 33.3) 9.9 NHL 18.6 (13.8 – 24.6) 10.7 32.7 (19.7 – 51.1) 27.8 Solid tumors Female breast Lung 2.4 (2.1 – 2.7) 2.5 (1.8 – 3.4) 4.2 (3.3 – 5.2) 29.3 11.3 13.5 3.6 (2.8 – 4.6) 4.6 (3.0 – 6.6) 7.3 (4.7 – 10.6) 74.4 39.5 33.8

RISK OF SECOND CANCERS

Van Leeuwen FE, J Clin Oncol 1994;12:312 Swerdlow AJ, Br Med J 1992;304:1137 Tucker MA, NEJM 1988;318:76

S Laskar ICARO 2009

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SECOND CANCERS ??????????????????

IJROBP 2003

S Laskar ICARO 2009

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Its 15 Years after the first clinical use of IMRT “NO REPORT OF 2ND MALIGNANCIES TILL DATE”

S Laskar ICARO 2009

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Lancet Oncology 2006

S Laskar ICARO 2009

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Lancet Oncology 2005

S Laskar ICARO 2009

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ISSUES……………..

Exact mechanism of radiation induced second cancers Which is more harmful ?? Low Dose Radiation High Dose Radiation Who is the culprit ?? Radiation Chemotherapy

S Laskar ICARO 2009

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IMRT!!

S Laskar ICARO 2009

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SUMMARY

Radiation therapy associated with both acute & late sequlae Severity influenced by: Patient Related/ Tumor Related/ Treatment Related Factors RT Related Acute Sequelae: Self Limiting RT Related Late Sequelae: Site Irradiated, Volume, Dose, Fractionation Concurrent Therapies Optimal Sequencing Essential for Favorable Outcome

S Laskar ICARO 2009

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Thank You

S Laskar ICARO 2009