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Outcomes Following Hypofractionated Radiotherapy for Patients with Thoracic Tumors in Predominantly Central Locations
Outcomes Following Hypofractionated Radiotherapy for Patients with Thoracic Tumors in Pred...
Outcomes Following Hypofractionated Radiotherapy for Patients with Thoracic Tumors in Predominantly Central Locations

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20250211151106
ISBN  
9798382328065
DDC  
610
저자명  
Sasse, Alexander William.
서명/저자  
Outcomes Following Hypofractionated Radiotherapy for Patients with Thoracic Tumors in Predominantly Central Locations
발행사항  
[Sl] : Yale University, 2024
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2024
형태사항  
57 p
주기사항  
Source: Dissertations Abstracts International, Volume: 85-11, Section: B.
주기사항  
Advisor: Park, Henry.
학위논문주기  
Thesis (M.D.)--Yale University, 2024.
초록/해제  
요약Hypofractionated radiation therapy (HFRT) is emerging as a preferred treatment for lung cancer patients ineligible for stereotactic body radiotherapy (SBRT). Normally, a standard-dose (SD-HFRT) hypofractionation regimen administers 60 Gy across 15 fractions, equating to a biologically effective dose (BED10) of 84.0, which is less than that of ablative SBRT. The first part of this thesis contrasts the clinical outcomes of patients receiving a high-dose (HD-HFRT) protocol, delivering 72 Gy in 18 fractions with a BED10 of 100.8, against those on SD-HFRT. Our research examines whether HD-HFRT enhances local control (LC) and overall survival (OS) rates while maintaining comparable rates of grade 3+ toxicity to SD-HFRT.Furthermore, the scarcity of data concerning dose-volume predictors for radiation pneumonitis and esophagitis under HFRT is notable, particularly given that existing guidelines predominantly reference conventional fractionation. This investigation seeks to pinpoint dosimetric risk factors tied to radiation pneumonitis in patients undergoing HFRT at 4 Gy per fraction. Key variables of interest include lung V20, mean lung dose (MLD), and lung V5, as potential indicators of grade ≥2 pneumonitis. Concurrently, our research evaluates the predictive capacity of esophageal V20, mean esophageal dose (MED), and esophageal V5 in forecasting the onset of grade ≥2 esophagitis.A retrospective database was created of all patients at our institution who received either thoracic SD-HFRT or HD-HFRT between 2013 and 2020. Data collection was done manually. Baseline variables were compared by chi-square analysis and logistic regression. We analyzed the association between treatment regimens with LC and OS (log-rank test and Cox proportional hazards regression), as well as grade 3+ toxicity. Data analysis was performed utilizing STATA.To summarize, our study has 3 primary aims:Aim 1: Compare the Two HFRT Regimens A total of 107 patients were included, among whom 55 (51.4%) received SD-HFRT and 52 (48.6%) received HD-HFRT. Median age was 73, 88.8% of patients had non-small cell lung cancer, 81.3% received lung-only treatment, and 52.3% had an ultra-central tumor location defined as abutting or within 1 cm of critical structures with 45.8% directly abutting one of these structures. Patients with HD-HFRT were more likely to have lung-only treatment (92.3% vs. 70.9%, p=0.005) and stage I disease (46.2% vs 23.6%, p=0.01) than those with SD-HFRT, but had a similar proportion of ultra-central tumors (57.1% vs. 54.9%, p=0.82). Among those with ultra-central tumors, patients with HD-HFRT had statistically significantly higher LC (2-year 86.6% vs 71.2%, 3-year 86.6% vs 42.2%, HR 0.26 [95% CI 0.08-0.84] p=0.02) and a non-statistically significant trend towards higher OS (2-year 63.8% vs 40.0%, 3-year 46.2% vs 31.1% HR 0.55 [95% CI 0.28-1.09] p=0.09) compared to those with SD-HFRT.Aim 2: Identify Dose-Volume Predictors of Grade 2+ Radiation PneumonitisOver a median 24.3-month follow-up, 18 patients (16.8%) developed grade ≥2 radiation pneumonitis, with no significant difference between the two dose regimens (17.3% vs. 16.3%, p=0.88). Four patients (3.7%) experienced grade ≥3 pneumonitis, including two grade 5 cases. Patients with grade ≥2 pneumonitis had significantly higher lung V20 (mean 23.4% vs. 14.5%, p0.001), MLD (mean 13.0 Gy vs. 9.5 Gy, p0.001), and lung V5 (mean 49.6% vs. 40.6%, p=0.01). Dose thresholds for a 20% risk of grade ≥2 pneumonitis were lung V20 17.7%, MLD 10.6 Gy, and V5 41.3%.Aim 3: Identify Dose-Volume Predictors of Grade 2+ EsophagitisTumors within 2 cm of the esophagus comprised 27.1% of total patients, and tumors within 1 cm of the esophagus comprised 10.3% of total patients. Median follow-up was 24.3 months. There were 13 cases (12.1%) of grade ≥2 esophagitis, with no statistically significant difference between 60 Gy and 72 Gy (9.4% vs. 14.8%, p=0.39). Three patients (2.8%) developed grade 3 esophagitis, with no cases of grade 4-5 esophagitis. When comparing patients who experienced a grade ≥2 esophagitis vs. those who did not, there was a statistically significant difference in esophagus Dmean (mean 13.8 Gy vs. 9.7 Gy, OR 1.11 [95% CI 1.01-1.23], p=0.02), esophagus Dmax (mean 45.8 Gy vs. 35.9 Gy, OR 1.05 [95% CI 1.00-1.09], p=0.03), and esophagus V40 (mean 5.5% vs. 2.3%, OR 1.10 [95% CI 1.01-1.21], p=0.04), but no statistically significant difference in esophagus V60 (mean 0.20% vs. 0.01%, OR 7.65 [95% CI 0.23-255.8], p=0.26).As HFRT becomes increasingly common for treatment of cancer across all disease sites (and in thoracic tumors especially), it is critical that the presentation and identification of patients that would benefit from these regimens is standardized and constraints found to mitigate their risk of side effects that can significantly affect their quality of life.
일반주제명  
Medicine
일반주제명  
Oncology
일반주제명  
Health sciences
키워드  
Hypofractionated radiation therapy
키워드  
Radiation oncology
키워드  
Thoracic tumors
기타저자  
Yale University Yale School of Medicine
기본자료저록  
Dissertations Abstracts International. 85-11B.
전자적 위치 및 접속  
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■1001  ▼aSasse,  Alexander  William.
■24510▼aOutcomes  Following  Hypofractionated  Radiotherapy  for  Patients  with  Thoracic  Tumors  in  Predominantly  Central  Locations
■260    ▼a[Sl]▼bYale  University▼c2024
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■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  85-11,  Section:  B.
■500    ▼aAdvisor:  Park,  Henry.
■5021  ▼aThesis  (M.D.)--Yale  University,  2024.
■520    ▼aHypofractionated  radiation  therapy  (HFRT)  is  emerging  as  a  preferred  treatment  for  lung  cancer  patients  ineligible  for  stereotactic  body  radiotherapy  (SBRT).  Normally,  a  standard-dose  (SD-HFRT)  hypofractionation  regimen  administers  60  Gy  across  15  fractions,  equating  to  a  biologically  effective  dose  (BED10)  of  84.0,  which  is  less  than  that  of  ablative  SBRT.  The  first  part  of  this  thesis  contrasts  the  clinical  outcomes  of  patients  receiving  a  high-dose  (HD-HFRT)  protocol,  delivering  72  Gy  in  18  fractions  with  a  BED10  of  100.8,  against  those  on  SD-HFRT.  Our  research  examines  whether  HD-HFRT  enhances  local  control  (LC)  and  overall  survival  (OS)  rates  while  maintaining  comparable  rates  of  grade  3+  toxicity  to  SD-HFRT.Furthermore,  the  scarcity  of  data  concerning  dose-volume  predictors  for  radiation  pneumonitis  and  esophagitis  under  HFRT  is  notable,  particularly  given  that  existing  guidelines  predominantly  reference  conventional  fractionation.  This  investigation  seeks  to  pinpoint  dosimetric  risk  factors  tied  to  radiation  pneumonitis  in  patients  undergoing  HFRT  at  4  Gy  per  fraction.  Key  variables  of  interest  include  lung  V20,  mean  lung  dose  (MLD),  and  lung  V5,  as  potential  indicators  of  grade  ≥2  pneumonitis.  Concurrently,  our  research  evaluates  the  predictive  capacity  of  esophageal  V20,  mean  esophageal  dose  (MED),  and  esophageal  V5  in  forecasting  the  onset  of  grade  ≥2  esophagitis.A  retrospective  database  was  created  of  all  patients  at  our  institution  who  received  either  thoracic  SD-HFRT  or  HD-HFRT  between  2013  and  2020.  Data  collection  was  done  manually.  Baseline  variables  were  compared  by  chi-square  analysis  and  logistic  regression.  We  analyzed  the  association  between  treatment  regimens  with  LC  and  OS  (log-rank  test  and  Cox  proportional  hazards  regression),  as  well  as  grade  3+  toxicity.  Data  analysis  was  performed  utilizing  STATA.To  summarize,  our  study  has  3  primary  aims:Aim  1:  Compare  the  Two  HFRT  Regimens  A  total  of  107  patients  were  included,  among  whom  55  (51.4%)  received  SD-HFRT  and  52  (48.6%)  received  HD-HFRT.  Median  age  was  73,  88.8%  of  patients  had  non-small  cell  lung  cancer,  81.3%  received  lung-only  treatment,  and  52.3%  had  an  ultra-central  tumor  location  defined  as  abutting  or  within  1  cm  of  critical  structures  with  45.8%  directly  abutting  one  of  these  structures.  Patients  with  HD-HFRT  were  more  likely  to  have  lung-only  treatment  (92.3%  vs.  70.9%,  p=0.005)  and  stage  I  disease  (46.2%  vs  23.6%,  p=0.01)  than  those  with  SD-HFRT,  but  had  a  similar  proportion  of  ultra-central  tumors  (57.1%  vs.  54.9%,  p=0.82).  Among  those  with  ultra-central  tumors,  patients  with  HD-HFRT  had  statistically  significantly  higher  LC  (2-year  86.6%  vs  71.2%,  3-year  86.6%  vs  42.2%,  HR  0.26  [95%  CI  0.08-0.84]  p=0.02)  and  a  non-statistically  significant  trend  towards  higher  OS  (2-year  63.8%  vs  40.0%,  3-year  46.2%  vs  31.1%  HR  0.55  [95%  CI  0.28-1.09]  p=0.09)  compared  to  those  with  SD-HFRT.Aim  2:  Identify  Dose-Volume  Predictors  of  Grade  2+  Radiation  PneumonitisOver  a  median  24.3-month  follow-up,  18  patients  (16.8%)  developed  grade  ≥2  radiation  pneumonitis,  with  no  significant  difference  between  the  two  dose  regimens  (17.3%  vs.  16.3%,  p=0.88).  Four  patients  (3.7%)  experienced  grade  ≥3  pneumonitis,  including  two  grade  5  cases.  Patients  with  grade  ≥2  pneumonitis  had  significantly  higher  lung  V20  (mean  23.4%  vs.  14.5%,  p0.001),  MLD  (mean  13.0  Gy  vs.  9.5  Gy,  p0.001),  and  lung  V5  (mean  49.6%  vs.  40.6%,  p=0.01).  Dose  thresholds  for  a  20%  risk  of  grade  ≥2  pneumonitis  were  lung  V20  17.7%,  MLD  10.6  Gy,  and  V5  41.3%.Aim  3:  Identify  Dose-Volume  Predictors  of  Grade  2+  EsophagitisTumors  within  2  cm  of  the  esophagus  comprised  27.1%  of  total  patients,  and  tumors  within  1  cm  of  the  esophagus  comprised  10.3%  of  total  patients.  Median  follow-up  was  24.3  months.  There  were  13  cases  (12.1%)  of  grade  ≥2  esophagitis,  with  no  statistically  significant  difference  between  60  Gy  and  72  Gy  (9.4%  vs.  14.8%,  p=0.39).  Three  patients  (2.8%)  developed  grade  3  esophagitis,  with  no  cases  of  grade  4-5  esophagitis.  When  comparing  patients  who  experienced  a  grade  ≥2  esophagitis  vs.  those  who  did  not,  there  was  a  statistically  significant  difference  in  esophagus  Dmean  (mean  13.8  Gy  vs.  9.7  Gy,  OR  1.11  [95%  CI  1.01-1.23],  p=0.02),  esophagus  Dmax  (mean  45.8  Gy  vs.  35.9  Gy,  OR  1.05  [95%  CI  1.00-1.09],  p=0.03),  and  esophagus  V40  (mean  5.5%  vs.  2.3%,  OR  1.10  [95%  CI  1.01-1.21],  p=0.04),  but  no  statistically  significant  difference  in  esophagus  V60  (mean  0.20%  vs.  0.01%,  OR  7.65  [95%  CI  0.23-255.8],  p=0.26).As  HFRT  becomes  increasingly  common  for  treatment  of  cancer  across  all  disease  sites  (and  in  thoracic  tumors  especially),  it  is  critical  that  the  presentation  and  identification  of  patients  that  would  benefit  from  these  regimens  is  standardized  and  constraints  found  to  mitigate  their  risk  of  side  effects  that  can  significantly  affect  their  quality  of  life.
■590    ▼aSchool  code:  0265.
■650  4▼aMedicine
■650  4▼aOncology
■650  4▼aHealth  sciences
■653    ▼aHypofractionated  radiation  therapy
■653    ▼aRadiation  oncology
■653    ▼aThoracic  tumors
■690    ▼a0564
■690    ▼a0566
■690    ▼a0992
■71020▼aYale  University▼bYale  School  of  Medicine.
■7730  ▼tDissertations  Abstracts  International▼g85-11B.
■790    ▼a0265
■791    ▼aM.D.
■792    ▼a2024
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17160723▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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