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j.ijrobp.2017.06.1288

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Volume 99 Number 2S Supplement 2017
The median total prescription radiation dose to the pelvis for IMRT was 50
Gy (36-66 Gy) and non-IMRT was 45 Gy (18-59.4 Gy) (pZ0.003). Of
those who reported toxicities, 9 (17%) patients experienced two or more
GU toxicities and 50 (70%) patients experienced two or more GI toxicities.
A total of 66 GU toxicities were observed with the greatest number seen at
week 4 (nZ15, 23%) and subsequently at week 3 (nZ14, 21%). Similarly,
a total of 235 GI toxicities were observed and majority was seen at week 4
(nZ80, 34%), subsequently at week 3 (nZ23, 20%), and at week 5
(nZ47, 20%). At week 4, there were 12% IMRT and 10% non-IMRT GU
toxicities, and 30% IMRT and 37% non-IMRT GI toxicities. There were no
statistically significant differences in the number of GU or GI toxicities at
week 3, 4, or 5 stratified by IMRT versus non-IMRT (all p>0.2).
Conclusion: Based on this observational analysis, there is an increase in
the number of GU and GI toxicities throughout a course of pelvic radiation
at week 4 for those treated with either IMRT or 3D radiation.
Author Disclosure: L.P. Cho: None. Z. Cheng: None. T.R. McNutt:
Research Grant; Elekta Oncology Systems, Philips Radiation Oncology
Systems, Toshiba. Patent/License Fees/Copyright; Accuray-Tomotherapy,
Sun Nuclear. 3-yr elected term from president elect to president to pastpresident.; AAPM-MAC. T.L. DeWeese: None. A.N. Viswanathan: None.
2683
Risk Factors of Radiation-Related Secondary
Malignancy in Pelvis after Radiotherapy for
Cervical Cancer: Multi-Institutional Study in Korea
E.C. Choi,1 Y.B. Kim,2 J.Y. Kim,3 Y.S. Kim,4 M. Chun,5 W. Park,6
H. Park,7 J.H. Lee,8 and J.H. Kim9; 1Department of Radiation Oncology,
Dongsan Medical Center, Keimyung University School of Medicine,
Daegu, Korea, Republic of (South), 2Yonsei Cancer Center, Yonsei
University College of Medicine, Seoul, Korea, Republic of (South),
3
Research Institute and Hospital, National Cancer Center, Goyang,
Gyeonggi, Korea, Republic of (South), 4Department of Radiation
Oncology, Asan Medical Center, University of Ulsan College of Medicine,
Seoul, Korea, Republic of (South), 5Department of Radiation Oncology,
Ajou University School of Medicine, Suwon, Korea, Republic of (South),
6
Samsung Medical Center, Sungkyunkwan University School of Medicine,
Seoul, Korea, Republic of (South), 7Presbyterian Hospital, Jeonju, Korea,
Republic of (South), 8Department of Radiation Oncology, St. Vincent’s
Hospital, The Catholic University of Korea College of Medicine, Suwon,
Korea, Republic of (South), 9Keimyung University Dongsan Medical
Center, Daegu, Korea, Republic of (South)
Purpose/Objective(s): This study aimed to assess the risk factors of radiation-related secondary malignancy in pelvis after radiotherapy for
cervical cancer.
Materials/Methods: We retrospectively reviewed 1564 patients who underwent radiation therapy for cervical cancer from 1985 to 2005 in 8 institutions. Most of patients were treated with external radiotherapy of
median 5400 cGy, with or without intracavitary radiotherapy of median
3000 cGy. Radiation-related secondary malignancy defined the followings:
(1) Malignancy developed in pelvis, at least 5 years after the end of
radiotherapy. (2) Pathology record of secondary malignancy was different
from that of primary cervical cancer, or malignancy originated from other
organ in pelvis. Of these patients, 88 patients were diagnosed with radiation-related secondary malignancy. 679 patients who did not develop
secondary cancer were analyzed using propensity score matching as a
control for risk factor analysis. Chi square test was used for comparison
between the two groups and logistic regression analysis was used for risk
factor analysis.
Results: Several factors were considered for the analysis. There was no
difference in the distribution between two groups. In univariate analysis,
intracavitary dose (<30Gy vs 30Gy, OR 0.444, 95% CI 0.243-0.811, p
Z 0.008), uterine dose (75Gy vs.> 75Gy, OR 2.042, 95% CI 1.2843.249; p Z0.003) and total dose (83Gy vs.> 83Gy, OR 0.550, 95% CI
Poster Viewing E287
0.351-0.861; p Z 0.009) were statistically significant factors. Paraaortic
lymph node (PAN) involvement (negative vs. positive, OR 0.168, 95% CI
0.023-1.235; pZ0.08) was marginally significant factor. In multivariate
analysis, all the parameters with a p-value of less than 0.1 were analyzed.
Pelvic lymph node involvement (negative vs. positive, OR 1.796, 95% CI
1.006-3.208; p Z 0.048), uterine dose (75 Gy vs.> 75 Gy , OR 3.652,
95% CI 2.102-6.344; p <0.001) and total dose (83 Gy vs.> 83 Gy, OR
0.367, 95% CI 0.209-0.645, p <0.001) were analyzed as significant risk
factors. Paraaortic lymph node involvement (negative vs. positive, OR
0.134, 95% CI 0.018-1.017; p Z 0.052) and intracavitary dose (<30 Gy
vs. 30 Gy, OR 0.516, 95% CI 0.262-1.015; pZ0.055) were marginally
significant. Other factors were not statistically significant.
Conclusion: In our analyses, the risk factors for radiation-related secondary malignancy were pelvic lymph node involvement, high uterine
dose, and low total radiation dose. Intracavitary dose and PAN involvement
may be considered as factors that may affect the occurrence of radiationrelated secondary malignancies. In particular, because high intracavitary
dose tends to reduce radiation-related secondary malignancy, external radiation dose may affect the occurrence of secondary malignancy.
Author Disclosure: E. Choi: None. Y. Kim: None. J. Kim: None. Y. Kim:
None. M. Chun: None. W. Park: None. H. Park: None. J. Lee: None. J.
Kim: None.
2684
Cisplatin and Gemcitabine Combined with Highly
Conformal External Beam Radiation Therapy in the
Treatment of Cervical Cancer Patients Result in
Low Toxicity and Promising Outcome
N. Cihoric,1 M. Glatzer,2 E. Vlaskou Badra,1 A. Tsikkinis,1 and K. Lössl1;
1
Department of Radiation Oncology, Inselspital, Bern University Hospital,
University of Bern, Bern, Switzerland, 2Department of Radiation
Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland
Purpose/Objective(s): Cisplatin and gemcitabine combined with conventional radiation therapy in treatment of cervical cancer patients results
in favorable outcome but excess toxicity. The purpose of this study was to
determine toxicity profile of dual chemotherapy and highly conformal
radiation therapy.
Materials/Methods: 17 patients with cervical carcinoma FIGO stage IB2
e IIIB were treated with curative intent between 2011 and 2015. The dose
of 50.4 Gy was prescribed to the elective pelvic nodal volume. Patients
with 18FDG-PET/CT positive lymph nodes (n Z 15; 83.3 %) received a
simultaneous integrated boost to a total dose of 62 Gy. Chemotherapy
prescription goals were: concomitant during 5 weeks of external beam
radiation therapy (EBRT) 40mg/m2 cisplatin and 125mg/m2 gemcitabine,
followed by adjuvant chemotherapy from week 10 (2 cycles 50mg/m2
cisplatin and 1000mg/m2 gemcitabine). EBRT was followed by 3 to 4
fractions (6 Gy) of 3D-HDR intrauterine brachytherapy. Toxicities were
graded according to the common terminology criteria for adverse events
(CTCAE v 4.0).
Results: Hematologic toxicity occurred mainly in form of grade 2 anemia
in 10 patients (59%) while neutropenia grade 3 was reported in only 1
patient (6%). Other hematologic toxicities higher than grade 2 did not
occur. One patient (6%) developed acute grade 3 diarrhea. Other gastrointestinal toxicities were not reported, neither were any other toxicities of
acute or chronic nature higher than grade 2. The number of patients
receiving complete chemotherapy regime declined gradually during course
of therapy. From week 2 to week 5 gemcitabine was omitted in 4 (24%),7
(41%), 8 (47%),12 (71%) and cisplatin in 2 (12%),3 (18%),1 (6%),7 (41%)
patients respectively. Adjuvant cycles of chemotherapy were omitted in 8
patients (47%). During median follow-up time of 20 months (5 to 63
months) 6 (35%) patients developed disease relapse, 5 (29%) of them in
form of systemic disease.
Conclusion: In contrast to previous findings cisplatin and gemcitabine in
combination with highly conformal radiotherapy has a low toxicity profile.
E288
International Journal of Radiation Oncology Biology Physics
Further studies are necessary to determine optimal dose and efficiency of
the proposed therapy concept.
Author Disclosure: N. Cihoric: owner; A web portal: www.clinicaltrial.co.
M. Glatzer: None. E. Vlaskou Badra: None. A. Tsikkinis: None. K.
Lössl: None.
were identified. Women treated with SIB technique to either one or both
parametria were included. Acute and late toxicities (defined by the CTCAE
v 4.0), recurrences (local, sidewall, and distant), and overall survival were
analyzed via the Kaplan Meier method.
Results: Forty-three women with bulky stage IB1-IVB cervical cancer
were treated with curative intent radiotherapy from May 2011 to June 2016
(IB1 nZ2, IB2 nZ7, IIB nZ22, IIIA nZ2, IIIB nZ9, IVB nZ1). All
women received external beam radiotherapy (EBRT) to the whole pelvis
(45-51.4 Gy/ 24-25 fractions) as well as a unilateral or bilateral parametrial
boosts (53.6-60 Gy/ 24-25 fractions) given with SIB technique. Nodal
disease received additional dose in 35 women (55-70 Gy/ 24-36 fractions).
All women except for one received concurrent cisplatin. At the conclusion
of EBRT, brachytherapy was delivered to a total goal EQD2 dose of 7587Gy. Median follow-up time was 25.2 months. Rates of acute grade 2
gastrointestinal (GI), genitourinary (GU), and hematologic (heme) toxicities were 39.5%, 7.0%, and 55.8% respectively; acute grade 3 toxicities
were 7.0%, 2.3%, and 16.3% respectively. There were no acute grade 4
toxicities. Two-year rates of late grade 2 GI and GU toxicities were
33.5% and 10.4% respectively; two-year late grade 3 toxicities were
12.0% and 6.2% respectively. There were two grade 4 GI toxicities, both
rectovaginal fistulas. Two-year overall survival and local control rates were
82.1% and 89.4% respectively. Univariate analysis showed a significant
association between late grade 3 GI toxicity and BT rectal D2cc dose
(pZ0.041, HRZ1.210, 95% CI 1.008-1.453). Patients with cumulative
rectal D2cc EQD2 dose 75Gy had a significantly higher rate of late grade
3 GI and GU sequelae compared to those <75Gy (66.7% vs. 2.5% with
pZ0.001 and 66.7% vs. 0% with pZ0.004, respectively).
Conclusion: IMRT-SIB is a feasible technique allowing for dose escalation
to the parametria and sidewall, with overall toxicity rates similar to conventional technique. Late GI toxicity appears to be highly dependent upon
cumulative rectal dose; when the rectal D2cc was below 75Gy EQD2,
toxicity rates were low. If SIB technique is considered in the low pelvis, it
may be prudent to consider strict adherence to rectal dose constraints at
brachytherapy.
Author Disclosure: L. Daley: None. O.I. Craciunescu: None. G. Suneja:
None. K. Light: None. A. Rodrigues: None. J.P. Chino: Partner; Duke
University Cancer Center. Research Grant; Varian Medical Systems.
Stock; NanoScint.
2685
Incidence of Mesorectal Nodal Metastasis in
Vaginal and Cervical Cancer: Its Clinical
Implication
F. Cordero,1 O.L. Burnett, III,1 M. McNamara,1 T. Weber,1 J. Zarzour,1
S. Jang,2 O.C. Barrett,1 and R.Y. Kim1; 1University of Alabama at
Birmingham, Birmingham, AL, 2University of Wisconsin, Madison, WI
Purpose/Objective(s): Conventional radiation fields for gynecologic
malignancies include the primary tumor and regional lymph nodes in the
pelvis. However, the mesorectum is not routinely assessed and usually is
avoided to limit treatment related toxicities. There is a previous case report
about mesorectal lymph node metastases (MRNM) in gynecologic cancers,
but to the best of our knowledge there is no reported data evaluating the
incidence of MRNM in this population. We would like to report our initial
findings on MRNM incidence in cervical and vaginal cancer.
Materials/Methods: A total of 31 patients sequentially evaluated for
radiotherapy of cervical or vaginal cancer within the last year were
reviewed. Three diagnostic radiologists retrospectively assessed all available pre-treatment imaging for positive nodal involvement in the pelvis,
including the mesorectum. Pelvic nodal metastasis was defined as 1 cm,
MRNM as 0.5 cm for CT and MRI scans. PET / CT scans generally were
considered positive with SUV max > 2.5. The relationship of MRNM
incidence with primary site, FIGO stage, other lymphatic involvement, and
histology were evaluated.
Results: Of the 31 patients, 25 cervical (Stage IB2: 5; Stage II: 8; Stage
III: 10; Stage IV: 2) and 6 vaginal (Stage I: 1; Stage II: 4; Stage III: 1)
cases were evaluated. Eighteen pre-treatment PET/CT, 15 CT and 5 MRI
scans were reviewed. Nineteen (61%) patients had positive pelvic nodal
metastasis. Four of the 31 patients were positive for MRNM, which constitutes 12.9% of all the reviewed patients and 21% of patients with other
pelvic nodal involvement. Of the patients with MRNM, two had cervical
cancer (both stage III) and two had vaginal cancer (one stage II and one
stage III). All patients with MRNM had squamous histology and had
presence of pelvic node involvement.
Conclusion: The incidence of MRNM was 12.9% of all reviewed patients
and 21.0% of all patients with pelvic lymphatic involvement. More
advanced disease and pelvic lymph node involvement are associated with
MRNM. Further investigation is ongoing.
Author Disclosure: F. Cordero: None. O.L. Burnett: None. M. McNamara: None. T. Weber: None. J. Zarzour: None. S. Jang: None. O.
Barrett: None. R.Y. Kim: None.
2686
Simultaneous Integrated Parametrial/Sidewall
Boosts for Cervical Cancer: Late Toxicity and
Outcomes.
L.A. Daley, O.I. Craciunescu, G. Suneja, K. Light, A. Rodrigues,
and J.P. Chino; Duke University Medical Center, Durham, NC
Purpose/Objective(s): The purpose of this study was to evaluate the
safety of intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the parametrium/paracervical tissue among women
with locally advanced cervical cancer.
Materials/Methods: In this IRB approved retrospective study, women with
intact cervical cancer treated in a single institution with definitive radiation
therapy followed by brachytherapy (BT) boost from 2011 through 2016
2687
Evaluation of Toxicity in Patients With Metastatic
and Recurrent Cervical Cancer Receiving
Bevacizumab after Pelvic Radiation Therapy with
HDR Brachytherapy
J. DeMasi,1 S. Kumar,2 and J.M. Feddock1; 1University of Kentucky
Department of Radiation Medicine, Lexington, KY, 2University of
Kentucky, Lexington, KY
Purpose/Objective(s): The current standard of care for recurrent or
metastatic cervical cancer (CA) includes treatment using multi-agent
chemotherapy plus bevacizumab. This combination has been shown to
improve overall survival and has potential for long term control in up to
15% of patients (pts). Bevacizumab (bev) is a VEGF inhibitor, and VEGF
is known to be involved in normal tissue repair following high dose radiation. The risk for severe bowel injuries following bev administration is
thought to be low. However, not much data exists regarding its true safety
when used in the immediate period following high dose rate brachytherapy
(HDR brachy). We present some cautionary data identifying the possibility
of higher than expected risks for severe toxicity in pts treated using bev
after curative therapy including pelvicRT and brachytherapy.
Materials/Methods: A retrospective review of pts treated for recurrent,
persistent or metastatic cervical CA with a regimen including bev after
completing definitive pelvicRT with weekly cisplatin and HDR brachy was
performed from 6/2009 to 1/2017. Bev was most commonly delivered
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