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Christian Sinclair, MD, FAAHPM
Gentiva Health Systems
Spring 2012
Credits and Creative Commons
 Adopted with permission from
 Jerry Baker, MD, Texas Oncology, Fort Worth, TX
 Originally...
Objectives
 Understand the fundamentals of radiation
therapy
 Manage commonly expected side effects from
radiation thera...
Questions
 I don’t understand how radiation works to treat
cancer. Can you explain it to me?
 In which clinical situatio...
Outline
 Conventional Radiation Therapy
 Psychology of A Radiation Oncologist
 Palliative Radiation Therapy
 Hospice c...
Fundamentals
 Curie’s discover Radium 1898
 Biologic effects of ionizing radiation
 1st ‘cure from radiation therapy 18...
Tissue Absorption
 At any energy, x-rays are attenuated by tissue
 Absorbed dose decreases with depth
 Early treatments...
Advances in WWII
 Higher energy tools
 Cobalt-60
 Linear accelerators
 Penetrating radiation
 Skin-sparing effect
 W...
Volume-dose relationship
Greater tumor volume
requires
greater radiation dose
Dose-Damage Relationship
Higher radiation dose
increases risk for
damage to normal tissues
Finding Balance
Benefit of tumor control
versus
Risk of normal tissue injury
Selectivity of radiation effect:
 Radiation damages DNA
 Leads to cell death
 Radiation not selective
 Variable DNA da...
Fractionation
 Small does of radiation over time
 Most cancers sensitive to fractionated XRT
 Normal tissues protected ...
3000 cGy in 15 fractions
(200 cGy/fraction)
≠
3000 cGy in 10 fractions
(300 cGy/fraction)
Late Effects - Hypofractionation
 Years
 Brain and spinal cord
 Fibrosis
 Bowel
 Months-years
 Lung tissue
 lymphed...
Benefits - Hypofractionation
 Radiation dose given quickly
 Faster tumor response
 Avoid multiple trips
Cancer Symptoms for XRT
 Bleeding
 Pain
 Obstruction – Airway/Visceral
 Spinal cord compression
 Impending fractures
...
Bone Metastases
 65-75% of advanced breast/prostate CA
 30-40% of advanced lung cancer
 Skeletal-related events: pain, ...
Bone Metastases
 Historically
 Palliative XRT fractionated daily over 2-3 weeks
 Over past 20 years
 9 large RCT (>400...
Longer courses of treatment to higher total doses remain the
most commonly use schedules in the United States. In a
survey...
RTOG 97-14 – Painful Bone
 Breast or Prostate cancer
 Painful bone mets
 Confirmed met by imaging
 Prognosis > 3 mos, ...
RTOG 97-14 Results
 1998-2002; 897 eligible patients
 56% weight-bearing site, 72% pain score 7-10 ( severe),
 27% rece...
Cancer Care Ontario 2004
 Practice guidelines
 “Where the treatment objective is pain relief, a
single 8 Gy treatment, p...
Intl Survey of Practice Patterns
 Rad Onc in ASTRO, CARO, RANZCR
 5 scenarios
 101 schedules recommended
 Median dose ...
RVU for XRT
 3D Conformal XRT - $6,000-10,000
 IMRT $12,000-20,000
10 vs. 1 Fraction
10 vs. 1 Fraction
Spinal Cord Compression
 Previous concern with large doses per fraction in
this setting (‘double injury’ of radiation and...
Pathologic/Impending Fracture
 Very little published data
 Case‐by‐case decision making for palliative
radiotherapy
 Pa...
Trivia: Bone Mets
 Response to radiotherapy is not related to
severity of pretreatment pain
 [Kirou‐Mauro A et al. Int J...
Lung Cancer
 Second to bone metastases in available
published data for hypofractionated
radiotherapy: 13 RCTs
 Short cou...
Pelvic (and other) Bleeding
 Single or hypofractionated regimens reported
effective in prospective and retrospective revi...
Gastrointestinal Cancers
 Retrospective studies suggest
hypofractionated radiotherapy is effective in:
 improving pain (...
Head/Neck Cancers
 Prospective and retrospective studies suggest
hypofractionated radiotherapy is effective in
improving ...
Brain Metastases
 Radiotherapy prolongs survival
 Steroids: 1-2 months median OS
 XRT: 4-6 months median OS (RTOG)
 Pr...
Medical Director Strategies
 Meet in advance of need with your local radiation
oncologist
 Conditional referrals: your g...
Rapid Access Palliative XRT
 Canadian approach:
 combining separate clinic visits
 hypofractionated radiotherapy
 2004...
Conclusions
 Hospices and palliative care programs are
providing care for patients with symptomatic
advanced cancers
 Pa...
Bibliography
Caissie A et al. Assessment of health-related quality of life with the European Organization
for Research and...
Bibliography - continued
Fairchild A et al. The rapid access palliative radiotherapy program: blueprint for initiation of
...
Bibliography - continued
George R et al. Interventions for the treatment of metastatic extradural spinal cord
compression ...
Bibliography - Continued
Lester JF, Macbeth FR, Toy E, Coles B. Palliative radiotherapy regimens for non-small cell
lung c...
Bibliography - continued
Lutz ST, Chow EL, Hartsell WF, Konski AA. A review of hypofractionated palliative
radiotherapy. C...
Bibliography - continued
Onsrud M, Hagen B, Strickert T. 10-Gy single-fraction pelvic irradiation for palliation and
life ...
Bibliography - continued
Rodrigues G et al. Consensus statement on palliative lung radiotherapy: third international
conse...
Bibliography – the end
Tanner C. Palliative radiation therapy for cancer. J Palliat Med. 2011 May;14(5):672-3. Epub
2011 A...
Radiation Therapy in Palliative Care Spring 2012
Radiation Therapy in Palliative Care Spring 2012
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Radiation Therapy in Palliative Care Spring 2012

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  • If printing a hand out you can exclude slides 41-48
    This
  • • At ANY energy, x-rays are
    attenuated by tissue so that
    absorbed dose decreases
    with depth
  • 􀂃 ↑ dose/fraction = ↑ risk late toxicity
    􀂃 ↓ dose/fraction = ↓ risk late toxicity
  • Longer courses of treatment to higher total doses remain the most commonly used schedules in the United States. In a survey of 268 radiation oncologists in the United States, the physicians were asked about the management of a patient with bone metastases from breast cancer. The respondents recommended a median dose of 30 Gy given in 10 fractions, none recommended fewer than 7 treatments.
  • Inclusion Criteria
    􀂄 Breast or prostate cancer
    􀂄 Painful bone metastasis (>5/10 on brief pain index)
    􀂄 Radiographic evidence of bone met at painful site
    RTOG 97-14 painful bone metastases
    􀂄 Life expectancy > 3 months, KPS ≥ 40
    􀂄 No prior surgery or XRT to that site
    􀂄 No change in systemic therapy for 30 days
    􀂄 Bisphosphonates OK; no radioisotopes for 30 days
    􀂄 No spinal cord compression; no fracture/impending fx
    􀂄 Skull, hands, feet excluded from study
  • ASTRO plenary presentation
    􀂄 RTOG 97-14:
    􀂇 Optimal patient population
    V lid t d i
    RTOG 97-14 painful bone metastases
    􀂇 Validated pain measures
    􀂇 Statistical power
    􀂇 Response definition clear
    􀂄 “800 cGy x 1 fraction is the new standard of
    care for palliation of painful bony metastases”

    Hartsell WF et al. J Natl Cancer Inst 2005;97:798-804
  • Deleted Wagoner 2008
  • Deleted Sanjob 2005, Deleted Spanos 1993
  • No differences in response rates
    among various schedules; quicker
    response seen with shorter courses
  • Transcript of "Radiation Therapy in Palliative Care Spring 2012"

    1. 1. Christian Sinclair, MD, FAAHPM Gentiva Health Systems Spring 2012
    2. 2. Credits and Creative Commons  Adopted with permission from  Jerry Baker, MD, Texas Oncology, Fort Worth, TX  Originally presented at the 2010 AAHPM Assembly  This talk is licensed under a Creative Commons Attribution-ShareAlike 3.0 Unported License.  With attribution and sharing alike, you are free:  to Share — to copy, distribute and transmit the work  to Remix — to adapt the work  to make commercial use of the work
    3. 3. Objectives  Understand the fundamentals of radiation therapy  Manage commonly expected side effects from radiation therapy  Identify three situations where palliative radiation may be effective in hospice patients
    4. 4. Questions  I don’t understand how radiation works to treat cancer. Can you explain it to me?  In which clinical situations is palliative radiation truly effective?  How do you decide how many treatments?  Does radiation have to be so expensive?  Any tips for working with a radiation oncologist, or for simplifying the radiation process for patients?
    5. 5. Outline  Conventional Radiation Therapy  Psychology of A Radiation Oncologist  Palliative Radiation Therapy  Hospice collaboration
    6. 6. Fundamentals  Curie’s discover Radium 1898  Biologic effects of ionizing radiation  1st ‘cure from radiation therapy 1899  1st radiation oncologists  Dermatologists  Low-energy, low-output machines
    7. 7. Tissue Absorption  At any energy, x-rays are attenuated by tissue  Absorbed dose decreases with depth  Early treatments for deep tumors overdosed superficial tissues
    8. 8. Advances in WWII  Higher energy tools  Cobalt-60  Linear accelerators  Penetrating radiation  Skin-sparing effect  Without advanced imaging treatment focused on tumors easily seen
    9. 9. Volume-dose relationship Greater tumor volume requires greater radiation dose
    10. 10. Dose-Damage Relationship Higher radiation dose increases risk for damage to normal tissues
    11. 11. Finding Balance Benefit of tumor control versus Risk of normal tissue injury
    12. 12. Selectivity of radiation effect:  Radiation damages DNA  Leads to cell death  Radiation not selective  Variable DNA damage repair  Normal tissues repair damage  Malignant cells do not repair well
    13. 13. Fractionation  Small does of radiation over time  Most cancers sensitive to fractionated XRT  Normal tissues protected by fractionation  ↑ dose/fraction = ↑ risk late toxicity  ↓ dose/fraction = ↓ risk late toxicity
    14. 14. 3000 cGy in 15 fractions (200 cGy/fraction) ≠ 3000 cGy in 10 fractions (300 cGy/fraction)
    15. 15. Late Effects - Hypofractionation  Years  Brain and spinal cord  Fibrosis  Bowel  Months-years  Lung tissue  lymphedema
    16. 16. Benefits - Hypofractionation  Radiation dose given quickly  Faster tumor response  Avoid multiple trips
    17. 17. Cancer Symptoms for XRT  Bleeding  Pain  Obstruction – Airway/Visceral  Spinal cord compression  Impending fractures  Wounds  Skin metastases
    18. 18. Bone Metastases  65-75% of advanced breast/prostate CA  30-40% of advanced lung cancer  Skeletal-related events: pain, fracture, compression, hypercalcemia  SRE’s impact on QOL  Mobility and functional wellbeing  Decrease ADL’s  Increase depression/anxiety  Increase opioid needs Costa L et al. Support Care Cancer 2008;16:879‐889
    19. 19. Bone Metastases  Historically  Palliative XRT fractionated daily over 2-3 weeks  Over past 20 years  9 large RCT (>4000 patients) all demonstrate effectiveness of single fraction courses Lutz ST et al. Cancer 2007;109:1462‐1470; Coia LR et al. IJROBP 1988;14:1261‐1269.
    20. 20. Longer courses of treatment to higher total doses remain the most commonly use schedules in the United States. In a survey of 268 radiation oncologists in the United States the physicians were asked about the management of a patient with bone metastases from breast cancer. The respondents recommended a median dose of 30 Gy given in 10 fractions, none recommended fewer than 7 treatments.
    21. 21. RTOG 97-14 – Painful Bone  Breast or Prostate cancer  Painful bone mets  Confirmed met by imaging  Prognosis > 3 mos, KPS ≥ 40
    22. 22. RTOG 97-14 Results  1998-2002; 897 eligible patients  56% weight-bearing site, 72% pain score 7-10 ( severe),  27% receiving bisphosphonates, 57% solitary site  Grade 2-4 toxicity: 17% (30 Gy) vs. 10% (8 Gy), p<.0001  Late toxicity: 4% overall, p=NS. Same path fx rates.  Median survival 9 months, 41% 1y-OS  Pain relief: (e.g., pain inventory, narcotic use, ambulation)  CR+PR 65% (1 fraction) vs. CR+PR 66% (10 fractions) p=NS  ASTRO plenary: “800 cGy x 1 fraction is the new standard of care for palliation of painful bony metastases”
    23. 23. Cancer Care Ontario 2004  Practice guidelines  “Where the treatment objective is pain relief, a single 8 Gy treatment, prescribed to the appropriate target volume, is recommended as the standard dose-fractionation schedule for the treatment of symptomatic and uncomplicated bone metastases.”  Survey (Ontario practitioners)  83% agreed with evidence interpretation  75% agreed approved of guideline Wu JS-Y et al. BMC Cancer 2004;4:71-78
    24. 24. Intl Survey of Practice Patterns  Rad Onc in ASTRO, CARO, RANZCR  5 scenarios  101 schedules recommended  Median dose 3000 cGy/10 fractions  US Rad Onc 3x the number of fractions for same indication Fairchild A et al. IJROBP 2009;75:1501‐1510
    25. 25. RVU for XRT  3D Conformal XRT - $6,000-10,000  IMRT $12,000-20,000
    26. 26. 10 vs. 1 Fraction
    27. 27. 10 vs. 1 Fraction
    28. 28. Spinal Cord Compression  Previous concern with large doses per fraction in this setting (‘double injury’ of radiation and physical injury to cord)  Cochrane Review  Ambulatory patient, stable spine: palliative radiotherapy (short course suffices in patients with predicted survival <6 months)  Non-ambulatory patient, paraplegia <48 hrs, survival > 3 mos, 1 area of spine involved: consider surgery  All others: palliative radiotherapy George R et al. Cochrane Database Syst Rev 2008;4:CD006716
    29. 29. Pathologic/Impending Fracture  Very little published data  Case‐by‐case decision making for palliative radiotherapy  Pain is better relieved with surgery/stabilization in some cases
    30. 30. Trivia: Bone Mets  Response to radiotherapy is not related to severity of pretreatment pain  [Kirou‐Mauro A et al. Int J Radiat Oncol Biol Phys 2008;71:1208‐1212]  Pain flare occurs in 10‐25% of patients treated with radiotherapy (1‐2 days post‐treatment); readily controlled/prophylaxed with steroids  [Hird A et al. Clin Oncol 2009;21:329‐335. Hird A et al. Int J Radiat Oncol Biol Phys 2009]  QOL improves after radiotherapy for bone mets (pain, anxiety, sense of well‐being)  [Chow E et al. Support Cancer Ther 2004;1:179‐184]
    31. 31. Lung Cancer  Second to bone metastases in available published data for hypofractionated radiotherapy: 13 RCTs  Short courses [800 cGy x 1; 800 cGy x2) and long courses of radiotherapy are comparable in relieving symptoms from advanced lung cancer (dyspnea, pain, hemoptysis, cough, SVC syndrome)  Total symptom score improved more with long courses (65.4% v. 77.1% at 1yr), and with a slight survival advantage (26.5% v. 21.7%) Fairchild 2008; Lester 2006; Salvo 2009
    32. 32. Pelvic (and other) Bleeding  Single or hypofractionated regimens reported effective in prospective and retrospective reviews (RTOG: 1000 cGy x 1‐3 monthly; RTOG: 370 cGy BID x 2 days repeated q3 wks x2‐3; 800 cGy weekly x 3)  Hemoptysis improved in ~ 80% pts  Pelvic bleeding improved in ~ 90‐100%  Cervix/vagina/vulvar/endometrial cancers  Bladder/prostate/urethral cancers  Colorectal cancer Onsrud 2001; Pereira 2004; Tinger 2001
    33. 33. Gastrointestinal Cancers  Retrospective studies suggest hypofractionated radiotherapy is effective in:  improving pain (86%)  bleeding (70%)  dysphagia (81%)  Acute nausea when treating upper abdomen may limit short courses  MDACC: 14 fractions (3500 cGy) used most commonly Kim 2008; Murakami 2008; Hashimoto 2009
    34. 34. Head/Neck Cancers  Prospective and retrospective studies suggest hypofractionated radiotherapy is effective in improving pain, bleeding, airway obstruction,  wound progression, hoarseness, otalgia, dysphagia/odynophagia  RTOG regimen: 370 cGy BID x 2 days, repeated q3 weeks up to 3 cycles  ‘Christie scheme’: 312 cGy x 12  AIIMS regimen: 400 cGy x 5 Agarwal 2008; Al-mamgani 2009; Chen 2008; Mohanti 2004
    35. 35. Brain Metastases  Radiotherapy prolongs survival  Steroids: 1-2 months median OS  XRT: 4-6 months median OS (RTOG)  Prevents death from neurologic progression  Reduces/resolves neurologic symptoms  200 cGy x 20  300 cGy x 10 (most common, ‘standard’)  400 cGy x 5  850 cGy x 2
    36. 36. Medical Director Strategies  Meet in advance of need with your local radiation oncologist  Conditional referrals: your group will refer patients when patient convenience is maximized and cost is controlled  Review cases with radiation oncologist prior to a formal consult (prevents unnecessary patient transfers)  Description of problem  Any available imaging  Records of previous cancer treatment ESPECIALLY PRIOR RADIATION RECORDS
    37. 37. Rapid Access Palliative XRT  Canadian approach:  combining separate clinic visits  hypofractionated radiotherapy  2004‐2008, >3200 pts treated  52% pts bone mets  Pain rapidly improved for >75% pts  100% patient satisfaction Fairchild A et al. Support Care Cancer 2009;17:163‐70
    38. 38. Conclusions  Hospices and palliative care programs are providing care for patients with symptomatic advanced cancers  Palliative radiotherapy is effective, with limited side effects, and benefits some of these patients, when . . .  . . . it is convenient  . . . it is reasonably priced  . . . it is available
    39. 39. Bibliography Caissie A et al. Assessment of health-related quality of life with the European Organization for Research and Treatment of Cancer QLQ-C15-PAL after palliative radiotherapy of bone metastases. Clin Oncol (R Coll Radiol). 2012 Mar;24(2):125-33. Epub 2011 Sep 13. PubMed PMID: 21917431. Chow E et al. Update on the systematic review of palliative radiotherapy trials for bone metastases. Clin Oncol (R Coll Radiol). 2012 Mar;24(2):112-24. Epub 2011 Nov 29. PubMed PMID: 22130630. Coia LR et al. Practice patterns of palliative care for the United States 1984-1985. Int J Radiat Oncol Biol Phys. 1988 Jun;14(6):1261-9. PubMed PMID: 2454905. Costa L etal. Impact of skeletal complications on patients' quality of life, mobility, and functional independence. Support Care Cancer. 2008 Aug;16(8):879-89. Epub 2008 Apr 8. Review. Erratum in: Support Care Cancer. 2008 Oct;16(10):1201. PubMed PMID: 18392862. Dennis K et al. Palliative radiotherapy for bone metastases in the last 3 months of life: worthwhile or futile? Clin Oncol (R Coll Radiol). 2011 Dec;23(10):709-15. Epub 2011 Jun 12. PubMed PMID: 21665446.
    40. 40. Bibliography - continued Fairchild A et al. The rapid access palliative radiotherapy program: blueprint for initiation of a one-stop multidisciplinary bone metastases clinic. Support Care Cancer. 2009 Feb;17(2):163-70. Epub 2008 Jun 20. PubMed PMID: 18566840. Fairchild A et al. Has the pattern of practice in the prescription of radiotherapy for the palliation of thoracic symptoms changed between 1999 and 2006 at the rapid response radiotherapy program? Int J Radiat Oncol Biol Phys. 2008 Mar 1;70(3):693-700. PubMed PMID: 18262087. Fairchild A et al. Palliative thoracic radiotherapy for lung cancer: a systematic review. J Clin Oncol. 2008 Aug 20;26(24):4001-11. Review. PubMed PMID: 18711191. Fairchild A, Chow E. Role of radiation therapy and radiopharmaceuticals in bone metastases. Curr Opin Support Palliat Care. 2007 Oct;1(3):169-73. Review. PubMed PMID: 18685358.
    41. 41. Bibliography - continued George R et al. Interventions for the treatment of metastatic extradural spinal cord compression in adults. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD006716. Review. PubMed PMID: 18843728. Hashimoto K et al. Palliative radiation therapy for hemorrhage of unresectable gastric cancer: a single institute experience. J Cancer Res Clin Oncol. 2009 Aug;135(8):1117- 23. Epub 2009 Feb 10. PubMed PMID: 19205735. Higginson DS et al.Predicting the need for palliative thoracic radiation after first-line chemotherapy for advanced nonsmall cell lung carcinoma. Cancer. 2011 Sep 20. doi:10.1002/cncr.26495. [Epub ahead of print] PubMed PMID: 21935913. Kim MM et al. Clinical benefit of palliative radiation therapy in advanced gastric cancer. Acta Oncol. 2008;47(3):421-7. PubMed PMID: 17899453.
    42. 42. Bibliography - Continued Lester JF, Macbeth FR, Toy E, Coles B. Palliative radiotherapy regimens for non-small cell lung cancer. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD002143. Review. PubMed PMID: 17054152. Lester JF, Macbeth FR, Brewster AE, Court JB, Iqbal N. CT-planned accelerated hypofractionated radiotherapy in the radical treatment of non-small cell lung cancer. Lung Cancer. 2004 Aug;45(2):237-42. PubMed PMID: 15246196. Loblaw DA, Mitera G, Ford M, Laperriere NJ. A 2011 Updated Systematic Review and Clinical Practice Guideline for the Management of Malignant Extradural Spinal Cord Compression. Int J Radiat Oncol Biol Phys. 2012 Mar 13. [Epub ahead of print] PubMed PMID: 22420969. Lutz S, Korytko T, Nguyen J, Khan L, Chow E, Corn B. Palliative radiotherapy: when is it worth it and when is it not? Cancer J. 2010 Sep-Oct;16(5):473-82. Review. PubMed PMID: 20890143.
    43. 43. Bibliography - continued Lutz ST, Chow EL, Hartsell WF, Konski AA. A review of hypofractionated palliative radiotherapy. Cancer. 2007 Apr 15;109(8):1462-70. Review. PubMed PMID: 17330854. Mehta RS, Arnold RM. Management of spinal cord compression #238. J Palliat Med. 2011 Mar;14(3):362-3. PubMed PMID: 21361838. Mitera G, Zhang L, Sahgal A, Barnes E, Tsao M, Danjoux C, Holden L, Chow E. A survey of expectations and understanding of palliative radiotherapy from patients with advanced cancer. Clin Oncol (R Coll Radiol). 2012 Mar;24(2):134-8. Epub 2011 Oct 2. PubMed PMID: 21963448. Murakami N, Nakagawa K, Yamashita H, Nagawa H. Palliative radiation therapy for advanced gastrointestinal cancer. Digestion. 2008;77 Suppl 1:29-35. Epub 2008 Jan 18. Review. PubMed PMID: 18204259.
    44. 44. Bibliography - continued Onsrud M, Hagen B, Strickert T. 10-Gy single-fraction pelvic irradiation for palliation and life prolongation in patients with cancer of the cervix and corpus uteri. Gynecol Oncol. 2001 Jul;82(1):167-71. PubMed PMID: 11426980. Paes FM, Ernani V, Hosein P, Serafini AN. Radiopharmaceuticals: when and how to use them to treat metastatic bone pain. J Support Oncol. 2011 Nov-Dec;9(6):197-205. Review. PubMed PMID: 22055888. Pereira J, Phan T. Management of bleeding in patients with advanced cancer. Oncologist. 2004;9(5):561-70. Review. PubMed PMID: 15477642. Reinfuss M, Mucha-Małecka A, Walasek T, Blecharz P, Jakubowicz J, Skotnicki P, Kowalska T. Palliative thoracic radiotherapy in non-small cell lung cancer. An analysis of 1250 patients. Palliation of symptoms, tolerance and toxicity. Lung Cancer. 2011 Mar;71(3):344-9. Epub 2010 Jul 31. PubMed PMID: 20674068.
    45. 45. Bibliography - continued Rodrigues G et al. Consensus statement on palliative lung radiotherapy: third international consensus workshop on palliative radiotherapy and symptom control. Clin Lung Cancer. 2012 Jan;13(1):1-5. doi: 10.1016/j.cllc.2011.04.004. Epub 2011 Jun 12. PubMed PMID: 21729656. Salvo N, et al. Quality of life measurement in cancer patients receiving palliative radiotherapy for symptomatic lung cancer: a literature review. Curr Oncol. 2009 Mar;16(2):16-28. PubMed PMID: 19370175; PubMed Central PMCID: PMC2669235. Salvo N et al. The role of plain radiographs in management of bone metastases. J Palliat Med. 2009 Feb;12(2):195-8. PubMed PMID: 19207068. Sundstrøm S et al. Hypofractionated palliative radiotherapy (17 Gy per two fractions) in advanced non-small-cell lung carcinoma is comparable to standard fractionation for symptom control and survival: a national phase III trial. J Clin Oncol. 2004 Mar 1;22(5):801-10. PubMed PMID: 14990635.
    46. 46. Bibliography – the end Tanner C. Palliative radiation therapy for cancer. J Palliat Med. 2011 May;14(5):672-3. Epub 2011 Apr 12. PubMed PMID: 21486147. Tinger A, Waldron T, Peluso N, Katin MJ, Dosoretz DE, Blitzer PH, Rubenstein JH, Garton GR, Nakfoor BA, Patrice SJ, Chuang L, Orr JW Jr. Effective palliative radiation therapy in advanced and recurrent ovarian carcinoma. Int J Radiat Oncol Biol Phys. 2001 Dec 1;51(5):1256-63. PubMed PMID: 11728685.
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