Hypoxia in clinical radiotherapy and methods to overcome it

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Hypoxia in clinical radiotherapy and methods to overcome it

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  • Conclusions by Thomlinson and Gray from studies on histological sections of human bronchial carcinoma showing the development of necrosis beyond a limiting distance from the vascular stroma
  • Hypoxia in clinical radiotherapy and methods to overcome it

    1. 1. TMHTATA MEMORIAL HOSPITAL HYPOXIA IN CLINICAL RADIOTHERAPY & METHODS TO OVERCOME IT Dr. Pramod Tike – JR I Dr. Indranil Mallick – SR IMonday, 2nd April 2007 DEPARTMENT OF RADIATION ONCOLOGY
    2. 2. TMHTATA MEMORIAL HOSPITALMECHANISM AND OXYGEN FIXATION HYPOTHESIS • Absorption of radiation • Fast charged particles produced • Passing through biologic material produce no. of ion pairs. • Free radical production • Breaks bonds • Produce chemical changes • This damage may be “fixed” by Oxygen -Hall, 1998 DEPARTMENT OF RADIATION ONCOLOGY
    3. 3. TMH TATA MEMORIAL HOSPITALTHE IMPORTANCE OF OXYGEN• “ The response of cells to ionization radiation is strongly dependent upon Oxygen”1• The enhancement of radiation damage by oxygen is dose modifying for same level of biological damage.• Oxygen Enhancement Ratio (OER) = Radiation damage in Hypoxia Radiation dose in air1.Grey et al 1953, Wright & Howard,Flanders 1957 DEPARTMENT OF RADIATION ONCOLOGY
    4. 4. TMHTATA MEMORIAL HOSPITALRADIATION DOSE MODYFYING EFFECT OF OXYGEN 10 Surviving fraction 1.0 Oxic Hypoxic 0.10 0.01 OER=2.8 0.001 0 5 10 15 20 25 30 35 Radiation dose Gy *with Xrays DEPARTMENT OF RADIATION ONCOLOGY
    5. 5. TMH TATA MEMORIAL HOSPITALRADIATION DOSE MODYFYING EFFECT OF OXYGEN 10Surviving fraction 1.0 Oxic Hypoxic 0.10 0.01 OER=1.6 *with 15 mev neutrons (OER=1.6) with α-rays (OER= 1.0) 0.001 0 5 10 15 20 25 30 35 Radiation dose Gy DEPARTMENT OF RADIATION ONCOLOGY
    6. 6. TMHTATA MEMORIAL HOSPITALVARIATION IN OER WITH OXYGEN TENSION O2 r Ai 200 re 400 600 Pu 800 (curve B) 3 OER 2 Venous Arterial 1 0 10 20 30 40 50 60 70 80 90 100 (curve A) Partial pressure of oxygen (mm Hg) DEPARTMENT OF RADIATION ONCOLOGY
    7. 7. TMHTATA MEMORIAL HOSPITALTUMOR VASCULATURE DEPARTMENT OF RADIATION ONCOLOGY
    8. 8. TMHTATA MEMORIAL HOSPITALDevelopment of microscopic regions of necrosis in tumors Stroma Viable tumor Necrosis 100 – 180 µm Conclusions by Thomlinson and Gray from studies on histological sections of human bronchial carcinoma showing the development of necrosis beyond a limiting distance from the vascular stroma DEPARTMENT OF RADIATION ONCOLOGY
    9. 9. TMH TATA MEMORIAL HOSPITALOXYGEN EFFECT• Impact of oxygen diffusion on radiation survival curve. DEPARTMENT OF RADIATION ONCOLOGY
    10. 10. TMHTATA MEMORIAL HOSPITALTUMOR HYPOXIA• Four different subpopulations of tumor cells with respect to oxygenation. – Well oxygenated viable & dividing – Well oxygenated viable & non-dividing – Poorly oxygenated viable & non-dividing – Anoxic and/or necrotic non-viable DEPARTMENT OF RADIATION ONCOLOGY
    11. 11. TMHTATA MEMORIAL HOSPITALTUMOR HYPOXIA• There are two types of hypoxia – Transient Hypoxia • Intermittent in nature • Can be quite severe – Permanent Hypoxia • Unrelieved hypoxia • Severe to the point of causing cell death DEPARTMENT OF RADIATION ONCOLOGY
    12. 12. TMHTATA MEMORIAL HOSPITALTUMOR HYPOXIA• Intermittent Hypoxia – Caused by vascular spasm – Spasm usually at the arteriole level – Due to lack or neurologic control of vessels – May be mediated by vasopressors secreted by the tumor – Increases radiation resistance – Increase resistance to some drugs DEPARTMENT OF RADIATION ONCOLOGY
    13. 13. TMHTATA MEMORIAL HOSPITALTUMOR HYPOXIA• Permanent Hypoxia – Occurs when tumor growth outstrips vascular supply – Hypoxic cells are physically displaced from vessels. – Oxygen diffusion distance varies with metabolism but beyond 100 microns hypoxia is probably profound. – Tumor pressure on surrounding tissues may further impede blood supply. DEPARTMENT OF RADIATION ONCOLOGY
    14. 14. TMHTATA MEMORIAL HOSPITALREOXYGENATION X-Rays X-Rays Aerated cells X-Rays 15% hypoxic cells n n tio io n at na Etc. io en e at yg yg en x eo ox yg R Re ox Re Mostly hypoxic cells DEPARTMENT OF RADIATION ONCOLOGY
    15. 15. TMHTATA MEMORIAL HOSPITALREOXYGENATION• Reoxygenation Fibrosarcoma patterns observed in preclinical tumor Osteosarcoma models treated with radiation.• Tannock and Hill, 1998. DEPARTMENT OF RADIATION ONCOLOGY
    16. 16. TMHTATA MEMORIAL HOSPITAL HYPOXIA IN CLINICAL PRACTICE DEPARTMENT OF RADIATION ONCOLOGY
    17. 17. TMHTATA MEMORIAL HOSPITALUTERINE CERVIX• Overall and disease-free survival probabilities for patients with advanced cancers of the uterine cervix treated with curative intent. – Hoeckel et al, 1996 DEPARTMENT OF RADIATION ONCOLOGY
    18. 18. TMH TATA MEMORIAL HOSPITALHb - HEAD & NECK CANCER• Effect of hemoglobin level on local – regional control in Head and Neck Cancer.• Overgaard et al, 1989 DEPARTMENT OF RADIATION ONCOLOGY
    19. 19. TMH TATA MEMORIAL HOSPITALHb - HEAD & NECK CANCER• Fein, D.A. et al - JCO 13:2077-2085, 1995 Local Control (%) Survival Hb < 13 g/dL (%) 66 46 T1 - T2 Glottic Ca p = .0018 p N = 109 < .001 95 88 Hb > 13 g/dL DEPARTMENT OF RADIATION ONCOLOGY
    20. 20. TMH TATA MEMORIAL HOSPITALBREAST• Oxygen tensions (pO2 frequency distributions) in normal breast and breast cancers.• Vaupel and Hoeckel, 1999 DEPARTMENT OF RADIATION ONCOLOGY
    21. 21. TMHTATA MEMORIAL HOSPITALSOFT TISSUE SARCOMA • Soft tissue sarcoma survival as a function of tumor oxygenation. – Brizel, 1999 DEPARTMENT OF RADIATION ONCOLOGY
    22. 22. TMHTATA MEMORIAL HOSPITALHYPOXIA IN TUMORS• Aggressiveness of Disease – Hypoxia may provide a mutant p53 growth advantage (Graeber et al., 1996). – In carcinoma of the cervix, patients with hypoxic tumors treated with surgery had a significantly worse disease-free and overall survival compared to patients with non-hypoxic tumors (Hoeckel et al., 1996). DEPARTMENT OF RADIATION ONCOLOGY
    23. 23. TMH TATA MEMORIAL HOSPITAL• Overall and disease-free survival probabilities in patients with advanced cancers of the uterine cervix treated with primary surgery.• Hoeckel et al., 1996 DEPARTMENT OF RADIATION ONCOLOGY
    24. 24. TMHTATA MEMORIAL HOSPITAL• Influence of tumor hypoxia on malignant progression. -Giaccia et al., 1999 DEPARTMENT OF RADIATION ONCOLOGY
    25. 25. TMHTATA MEMORIAL HOSPITALHYPOXIA IN TUMORS• Metastatic Spread – Hypoxic exposure of tumor cells in vitro can increase metastases in mice (Young et al., 1988). – Increased metastases can occur in mice with primary hypoxic tumors (De Jaeger et al., 2001). – The probability of distant metastases in soft tissue sarcoma was twice as great for tumors with median pO2 values < 10 mm Hg than for those with median pO2 values > 10 mm Hg (Brizel et al., 1996). DEPARTMENT OF RADIATION ONCOLOGY
    26. 26. TMH TATA MEMORIAL HOSPITALANEMIA AND TUMOR HYPOXIA• Hypoxic tumors are more likely to recur loco regionally than well oxygenated tumors regardless of whether Sx or RT is primary local treatment. – Hockel et al,Hypoxia and radiation response in in human tumors. Semin in rad onco 1996;6:3-9• Hockel et al reported Higher 5 yr DFS in pts in which median oxygenation measured with polarographic needles was atleast 10mmHg as compared to pts. With Po2 <10mmHg.• Higher incidence of pelvic rec. & lower survival rates in anemic pts treated with RT – Evans and Bergsjo et al(1965),Vigario et al(1973),• Milosevic et al (IJROBP 1999;43:1111-1123) showed decrease in tumor oxygenation related to increase in blood viscosity. DEPARTMENT OF RADIATION ONCOLOGY
    27. 27. TMH TATA MEMORIAL HOSPITALANEMIA AND TUMOR HYPOXIA• Blood transfusions in pts with Hb < 10 g/dL showed significant improvement in outcome ( Bush et al; Br J Canc1978;37:302-306)• Threshold for transfusion based on anemia during treatment and not initial Hb level ( Fyles et al; Radiother Oncol 2000;57:13-19) Will BT to Hb levels above 12-12.5 g/dL improve prognosis??• Retrospective reviev of 600 pts t/t for Ca Cx(Grogan et al:The importance of Hb levels during RT for Ca Cx; cancer 1999;86:1528-1536) Giving BT to maintaining avg. Hb level at that level during t/t is beneficial regardless the Hb at presentation DEPARTMENT OF RADIATION ONCOLOGY
    28. 28. TMH TATA MEMORIAL HOSPITALMETHODS FOR MEASUREMENT OF TUMOR HYPOXIA• Polarographic needles• Eppendorf probes• Molecular imaging DEPARTMENT OF RADIATION ONCOLOGY
    29. 29. TMHTATA MEMORIAL HOSPITAL HOW TO OVERCOME HYPOXIA ?? DEPARTMENT OF RADIATION ONCOLOGY
    30. 30. TMH TATA MEMORIAL HOSPITALHOW TO REDUCE HYPOXIA• Fractionation• Hyperbaric oxygen• Hypoxic cell sensitizers• Improving oxygenation of tumour – Blood transfusion – Perfluoro carbons – Nicotinamide – Carbogen+nicotinamide – Angiotensin II – Flunarizine DEPARTMENT OF RADIATION ONCOLOGY
    31. 31. TMHTATA MEMORIAL HOSPITALHYPOXIC SENSITIZERS• Misonidazole• Etanidazole• Pimanidazole• RSU-1069• Nimorazole (SER 1.3, +ve for head and neck and cervix)• AK 2123• Hyperthermia• RSR 13 (Banoxantrone)*• Motexafin Gadolinium*• HIF-1 Inhibitor* * Redox modulator in development, not approved by FDA yet DEPARTMENT OF RADIATION ONCOLOGY
    32. 32. TMH TATA MEMORIAL HOSPITALHYPOXIC SENSITIZERS Sensitizer Side Chain Advantages over misonidazoleSR 2508 CH2NHCOCH2CH2OH Decreased lipophilicityEtanidazole Shorter half life Lesser concn in brainRO 03 8799 CH2CH(OH)CH2N More electron affinic and better sensitizer (x3) Uncharged at acidic PH, and hence higher tumour concentration (X 1.6)RSU-1069 CH2CH(OH)CH2N Better sensitizer, bifunctional agent and hence highly toxic to hypoxic cells less Neurotoxic but GI toxicRO-07-0582 CH2CH(OH)CH2OCH3 Neurotoxic and hence cannot be used in radiotherapy DEPARTMENT OF RADIATION ONCOLOGY
    33. 33. TMHTATA MEMORIAL HOSPITALTO INCREASE HYPOXIA• BW12C• Hydralazine• Photodynamic therapy to destroy blood vessels DEPARTMENT OF RADIATION ONCOLOGY
    34. 34. TMHTATA MEMORIAL HOSPITALEFFECT OF FRACTIONATION• administering smaller dose fractions• oxygen effect is less profound at low doses. Thus hypoxic tumour cells would be less radioresistant.• If there is sufficient reoxygenation between fractions, a small hypoxic tumour subpopulation would have less influence on response to a sequence of small dose fractions as compared to high dose fractions DEPARTMENT OF RADIATION ONCOLOGY
    35. 35. TMHTATA MEMORIAL HOSPITALOXYGEN• First radiation sensitizer used clinically• Studies revealed the presence of necrotic zones in human tumours and animal testing demonstrated that 1% to 50% of the clonogenic cells in solid tumours could be radioresistant as a result of hypoxia. DEPARTMENT OF RADIATION ONCOLOGY
    36. 36. TMHTATA MEMORIAL HOSPITALHBOT• Hyperbaric oxygen chambers were used to tackle the problem of hypoxia.• Infeasible because of cumbersome procedure, time involved and fear of accident.• Patient’s compliance• Several clinical trial performed using oxygen as radiosensitiser failed to show significant improvement in survival. DEPARTMENT OF RADIATION ONCOLOGY
    37. 37. TMHTATA MEMORIAL HOSPITALBLOOD TRANSFUSIONS• BT to maintaining higher Hb improves outcome• Recombinant human erythropoietin (EPO): an alternative means of raising Hb during radiotherapy• Dose: 200 U/kg/day X 5 days/week expected to elevate Hb by an average of 1-3 g/dL ( Dusenbery et al;IJROBP;1994:29, Lavey et al;IJROBP;1993:27, Vijaykumar S;IJROBP;1993:26)• Induces prompt reticulocyte response from 2.4% to 4.9%• No proof that EPO is superior to BT with impact on clinical outcome.• Expensive than BT. DEPARTMENT OF RADIATION ONCOLOGY
    38. 38. TMHTATA MEMORIAL HOSPITALNICOTINAMIDE AND CARBOGEN BREATHING• To overcome the vasoconstriction caused by pure oxygen and to improve the blood supply to tumour hence to reduce the chronic hypoxia• Nicotinamide, vit.B3 prevents transient fluctuation in tumour blood flow hence reducing the acute hypoxia. DEPARTMENT OF RADIATION ONCOLOGY
    39. 39. TMH TATA MEMORIAL HOSPITALARCON• Accelerated hyper fractionated radiation therapy while breathing carbogen and with the addition of nicotinamide.• Strategy was to accelerate treatment to avoid tumor proliferation, hyper fractionate to minimize late effects and add carbogen breathing to overcome chronic hypoxia and nicotinamide to overcome acute hypoxia.• Early results of a trial of ARCON in Netherlands involving advanced laryngeal cancers showed spectacular results.• Results of a prospective randomized control trial are yet to be published. DEPARTMENT OF RADIATION ONCOLOGY
    40. 40. TMHTATA MEMORIAL HOSPITALHYPOXIC RADIOSENSITIZERS• Instead of forcing oxygen into hypoxic cells by use of high pressure tanks, the approach shifted to oxygen substitutes• These compounds get selectively activated in the hypoxic environment of tumour cells DEPARTMENT OF RADIATION ONCOLOGY
    41. 41. TMHTATA MEMORIAL HOSPITALCHARACTERISTICS OF HYPOXIC CELL SENSITIZERS• Selective sensitivity to hypoxic cells at a concentration that would result in acceptable toxicity to normal tissue.• Chemical stability and not subject to rapid metabolic breakdown.• Must be highly soluble in water or lipid and must be capable of diffusing considerable distance.• It should be effective at relatively low daily doses of few grays . DEPARTMENT OF RADIATION ONCOLOGY
    42. 42. TMHTATA MEMORIAL HOSPITALMISONIDAZOLE (LAB EXP.)• Hypoxic cells in presence of 10nM of misinidazole have radiosensitivity approaching to that of aerated cells. DEPARTMENT OF RADIATION ONCOLOGY
    43. 43. TMH TATA MEMORIAL HOSPITALMISONIDAZOLE CLINICAL-EXP• 20 or so randomized prospective controlled clinical trials failed to show a statistically significant advantage.• Only trial which showed advantage for Misonidazole was from Denmark• Dose limiting toxicities were peripheral neuropathy that progress to CNS toxicity if the drug is not stopped. DEPARTMENT OF RADIATION ONCOLOGY
    44. 44. TMH TATA MEMORIAL HOSPITALETANIDAZOLE• The compound equals to misonidazole as a sensitizer but is less toxic.• Dose factor could be increased by 3.• Shorter half life and lower partition coefficient so does not cross BBB.• Controlled trial by RTOG in US and a multicenter consortium in Europe showed no benefit from Etanidazole. DEPARTMENT OF RADIATION ONCOLOGY
    45. 45. TMH TATA MEMORIAL HOSPITALNIMORAZOLE• Less effective as a radiosensitiser but much less toxic• Very large doses could be given• In a Danish head and neck trial this compound showed a significant improvement in both locoregional control and survival compared with radiotherapy alone. DEPARTMENT OF RADIATION ONCOLOGY
    46. 46. TMHTATA MEMORIAL HOSPITAL DEPARTMENT OF RADIATION ONCOLOGY
    47. 47. TMH TATA MEMORIAL HOSPITAL• 422 patients were accrued• Median time 112 months DEPARTMENT OF RADIATION ONCOLOGY
    48. 48. TMHTATA MEMORIAL HOSPITALRESULTS• Locoregional control was 49% v/s 33% p=0.002• Same trend was also found in overall survival, but not to the significant extent 26% v/s 16% p= 0.32• Conclusion – Nimorazole significantly improves effect of radiotherapy managemant of supraglotic and pharynx tumour and can be given without major side effects DEPARTMENT OF RADIATION ONCOLOGY
    49. 49. TMH TATA MEMORIAL HOSPITALn=61 pts , (StgIII=21, StgIV=40) of Advanced SCC H&N, Unsuitable for Sxcontinuous hyperfractionated accelerated radiation therapy (CHART)+NimorazoleRT=56.75 Gy/36#/12 consecutive days @ 157.64Gy/#Nimorazole=orally or enterally 90 min before radiotherapy at a dose of 1.2, 0.9, and 0.6 g/m2with the first, second and third daily fractions,respectively.Loco-regional control at 2 years is 55%(StgIII=62%&StgIV=50%)slight increase in acute skin reaction than previovs CHARTNimorazole Toxicity was somewhat greater than those with once daily administration.Grade 3 nausea/vomiting occurred in 22% of pts. 2 pts developed grade 1 peripheral neuropathy1 pt. died during t/t of encephalopathy. DEPARTMENT OF RADIATION ONCOLOGY
    50. 50. TMHTATA MEMORIAL HOSPITAL RT= 62-68Gy/31-34# @ 2Gy/# & 5#/week Nimorazole= 1.2mg/m2 90 min before RT during first 30#s Placebo = Gelatine capsules DEPARTMENT OF RADIATION ONCOLOGY
    51. 51. TMHTATA MEMORIAL HOSPITAL DEPARTMENT OF RADIATION ONCOLOGY
    52. 52. TMHTATA MEMORIAL HOSPITAL DEPARTMENT OF RADIATION ONCOLOGY
    53. 53. TMHTATA MEMORIAL HOSPITALAK-2123 (Sanazol) DEPARTMENT OF RADIATION ONCOLOGY
    54. 54. TMH TATA MEMORIAL HOSPITALAK-2123 (Sanazol) Local Tx control actuarial survival at 60 months RT+ AK2123 Initial n=462 4 centres excluded 61% 57% n=3337 pts did not undergo t/t Finally (p = 0.006) (p = 0.01) n=326 evaluated 46% 41% Ca Cx IIIa+IIIb RT AloneRT= total dose of 45–50.8 Gy/20–28/4–5.5 weeks, with further dose escalation bybrachytherapy or external beamAK-2123 = 0.6 g/m2 intravenous administration before external beam radiotherapy onalternate days. DEPARTMENT OF RADIATION ONCOLOGY
    55. 55. TMH TATA MEMORIAL HOSPITALHYPOXIC CYTOTOXINS• Greater reductive environment of tumour might be exploited by developing drug that are reduced preferentially to cytotoxic species in hypoxic regions of tumour. DEPARTMENT OF RADIATION ONCOLOGY
    56. 56. TMH TATA MEMORIAL HOSPITALHYPOXIC CYTOTOXINS• Quinolone antibiotics eg.Mitomycin C• Nitroaromatic compounds• Benzotriazine di-N-oxides eg. Tirapazamine• AQ4N* DEPARTMENT OF RADIATION ONCOLOGY
    57. 57. TMH TATA MEMORIAL HOSPITAL• Vienna HFA-RCT study showed• Acturial overall survival 81% at one year,52%at two year and 33% at three year• Locoregional controll-61%,55%,55%• Radiation dose 64Gy (36Gy + 28Gy off cord)• Mitomycin-C i.v. bolus over 10 min 20mg/m2 on day 5 of RT DEPARTMENT OF RADIATION ONCOLOGY
    58. 58. TMHTATA MEMORIAL HOSPITALGERMAN ARO 95-6 TRIAL 4 YrSurvival (%) 4 Yr dose escalated HFRT 77.6Gy LRC(%) 28 40 N = 373 34 HFRT 70.6Gy + concurrent Mitomycin-C 50 Both the arms were equal regarding the acute and late toxicities. DEPARTMENT OF RADIATION ONCOLOGY
    59. 59. TMHTATA MEMORIAL HOSPITALPatients with advanced head and neck cancer were treated withprimary curative radiotherapy (66 Gy in 33fractions with five fractionsper week) ±a single injection (15 mg/m2) of MMC at the end of thefirst week of radiotherapy. DEPARTMENT OF RADIATION ONCOLOGY
    60. 60. TMH TATA MEMORIAL HOSPITALSCC of the oral cavity (n = 230), oropharynx(n = 140), hypopharynx (n = 65) or larynx (n = 43) N=161N0 66Gy/33#/6.5weeks 3 Yr LRC (%) 3Yrs LRC(%) 18 16 N = 478 P=0.01 Stage III=223 Stage IV=255 21 29 66Gy/33#/6.5weeks + concurrent Mitomycin-CConclusions: The study did not show any major influence of MMC on loco-regional tumourcontrol, survival or morbidity after primary radiotherapy in stage III–IV head and neck cancerexcept in N0 patients where loco-regional control was significantly improved. DEPARTMENT OF RADIATION ONCOLOGY
    61. 61. TMH TATA MEMORIAL HOSPITALTIRAPAZAMINE• TPZ is a benzotriazine compound that exhibits selective cytotoxicity for hypoxic cells.• Little clinical when used alone because the problem of nausea, vomiting, diarrhea and sever muscle cramping.• Various combinations studied – Cisplat alone Vs Cisplat+TPZ :(CATAPULT I;2000) – Cisplat+TPZ Vs cisplat+etoposide : (international phase III CATAPULT trial;2000) – Cisplat+TPZ+Fluorouracil Vs cisplat+fluorouracil : (Pro Am Soc Clin Oncol 2002;21:227a) – Cisplat+TPZ Vs cisplat+fluorouracil :(phase II trial TROG group;2005) – Paclitaxel/Carboplat (PC) Vs PC+ Tirapazamine (PCT): (phase III SWOG trial;2003) DEPARTMENT OF RADIATION ONCOLOGY
    62. 62. TMH TATA MEMORIAL HOSPITAL• Initial phase III study(n= 440) with advanced NSCLC treated with cisplatin alone Vs Cisplat+TPZ (CATAPULT I) showed positive results: Cisplat (75mg/m2) Vs Cisplat (75mg/m2)+TPZ(390mg/m2) Response rate 14% 27.5% Overall survival 8 months 6 months 1 Yr survival 33% 22%• Unfortunately, the follow-up study [CATAPULT II]failed to demonstrate similarsurvival advantagesTPZ (390 mg/m2) + cisplatin (75mg/m2) Vs etoposide (100 mg/m2) plus cisplatin (75 mg/m2). The TPZ-containing arm proved to be more toxic and less effective.•third phase III trial :TPZ ± paclitaxel/carboplatin in patients with advanced NSCLC.(SWOG0003) PC Vs PC+TPZ Overall survival 8 months 11 months (37% improvement) did not result in improved response, time to progression DEPARTMENT OF RADIATION ONCOLOGY
    63. 63. TMHTATA MEMORIAL HOSPITALTIRAPAZAMINE DEPARTMENT OF RADIATION ONCOLOGY
    64. 64. TMHTATA MEMORIAL HOSPITALHYPERTHERMIA• Mild hyperthermia can improve the tumour reoxygenation, with the degree of reoxygenation correlating with the level of cytotoxicity.• In addition to antitumour effect of heat, it has synergistic effect with radiation DEPARTMENT OF RADIATION ONCOLOGY
    65. 65. TMHTATA MEMORIAL HOSPITAL MOLECULAR PROFILING DEPARTMENT OF RADIATION ONCOLOGY
    66. 66. TMHTATA MEMORIAL HOSPITAL DEPARTMENT OF RADIATION ONCOLOGY
    67. 67. TMHTATA MEMORIAL HOSPITALBIOLOGICAL TARGET VOLUME/ BIOLOGICAL EYE VIEWBiological tumor volume – Derived from biological images and their use may guidecustomized dose delivery to various parts of treatment volume. DEPARTMENT OF RADIATION ONCOLOGY
    68. 68. TMHTATA MEMORIAL HOSPITAL DEPARTMENT OF RADIATION ONCOLOGY
    69. 69. TMHTATA MEMORIAL HOSPITAL Thank You! DEPARTMENT OF RADIATION ONCOLOGY
    70. 70. TMHTATA MEMORIAL HOSPITAL DEPARTMENT OF RADIATION ONCOLOGY
    71. 71. TMHTATA MEMORIAL HOSPITAL DEPARTMENT OF RADIATION ONCOLOGY
    72. 72. TMHTATA MEMORIAL HOSPITAL DEPARTMENT OF RADIATION ONCOLOGY

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