110 Post-Operative Low Pelvic Irradiation for Stage I-IIA Cervical

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					                                       Proceedings of the 43rd Annual ASTRO Meeting                                                  63

110      Post-Operative Low Pelvic Irradiation for Stage I-IIA Cervical Cancer Patients Who Have Pathological
         Risk Factors Other than Pelvic Lymph Node Metastasis

J.H. Hong1, C.S. Tsai1, C.C. Wang1, C.H. Lai2, T.C. Chang2, J.T. Chang1, C.J. Tseng2
  Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan, 2Gynecological
Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan

Purpose: To retrospectively investigate if the low pelvic irradiation is an appropriate method for stage I and IIA cervical cancer
patients who have pathological risk factors other than lymph node metastasis and are treated by post-operative radiotherapy (RT).
Materials and Methods: From Jan. 1990 to Dec. 1997, two hundred and twenty eight stage I-IIA cervical cancer patients
treated by radical surgery and post-operative RT were included in this study. They didn’t have pelvic node metastasis but have
one or more pathological risk factors including invasion depth 2/3 stromal thickness, parametrial involvement, positive
resection margin and lymphovascular permeation. Seventy-nine (35%) patients received 30-50 Gy (median: 44 Gy) to whole
pelvis and boost dose to low pelvis, and the rest 149 patients received low pelvic RT only. The external radiation dose to low
pelvis ranged from 40 to 60 Gy (median: 50 Gy). The length of the cephalic-caudal direction at the mid-plane is 10-14 cm
(median: 12 cm) and 15-21 cm (median: 18 cm) for low pelvis and whole pelvis field, respectively. Prognostic factors associated
with the survival, small bowel (GI) complications and lymphedema of leg were analyzed and patients who had a relapse in the
upper pelvis were identified.
Results: The five-year overall and disease-specific survival is 84% and 86%, respectively. After univariate and multivariate
analysis, only bulky tumor ( 4 cm), non-squamous cell carcinoma and positive resection margin are identified as independent
prognostic factors for survival. Parametrial involvement, lymphovascular invasion, radiation dose to low pelvis ( 50.4 Gy) and
low pelvic RT alone don’t significantly affect survival. Radiation dose ( 50.4 Gy) and whole pelvic RT are significantly
associated with grade I-IV GI complications, but old age, treatment technique (AP/PA vs. Box) aren’t. Radiation dose and
treatment technique are associated with lymphedema of leg, but whole pelvic RT, age and number of sampled lymph nodes
aren’t. Five (3.4%) cases in patients treated with low pelvic RT alone and none in patients treated by whole pelvic RT were
found to have a relapse in the upper pelvis. However, only 2 out of 149 (1.3%) cases treated by low pelvic RT alone have upper
pelvis relapse but no other distant metastasis. Three (2 %) cases in patients treated by low pelvic RT alone and 6 (8%) cases
in patients treated by whole pelvic RT were found to have grade III small bowel complications.
Conclusion: Compared to whole pelvic irradiation, low pelvic irradiation alone can significantly reduce the small bowel
complications in stage I and IIA cervical cancer patients who have pathological risk factors other than lymph node metastasis
and are treated by post-operative RT. However, it doesn’t reduce the incidence of lymphedema of leg. Although it increases
the possibility of upper pelvis relapse, only 1% patients treated by low pelvic irradiation alone had upper pelvic relapse without
distant failure. Low pelvic irradiation alone did not compromise patients’ survival and should be considered as an appropriate
method for this group of patients.

111      Phase I/II Results Using Concurrent Hyperthermia, Radiotherapy, and Chemotherapy for Cervix Cancer
E. Jones , D. Brizel1, M. Dewhirst1, A. Alvarez2, A. Berchuck2, D. Clarke-Pearson2, G. Rodriquez2, J. Soper2, L. Prosnitz1
  Radiation Oncology, Duke University Medical Center, Durham, NC, 2Gynecologic Oncology, Duke University Medical
Center, Durham, NC

Purpose: To evaluate toxicity and response in patients with advanced cervix cancer treated with concurrent weekly cisplatin
(CDDP), hyperthermia (HT), and radiation (RT).
Materials and Methods: From August 1998 through December 2000, 12 patients with bulky advanced cervix cancer or
recurrent cervix cancer were enrolled on a protocol combining weekly CDDP, HT and RT. The median age was 52 years (range
34 – 65). Two patients were treated for pelvic recurrences following hysterectomy alone. The FIGO stage and tumor diameter
for the remaining 10 patients treated at the time of diagnosis were as follows:
(n 2) IB 9 cm, IB 7 cm with para aortic nodes on CT
(n 1) IIA, 7 cm
(n 4) IIB, 5 cm, 6 cm, 7 cm, 8 cm
(n 3) IIIB 6 cm (2 patients), 7 cm
Three of the 12 patients had adenocarcinoma histology, all others were squamous cell.
Chemotherapy consisted of weekly CDDP given weekly (40 mg/m2) with standard hydration and antiemetic premedications.
All patients received external beam radiotherapy to the whole pelvis and para aortic nodes (if clinically involved) to a total of
45 – 50.4 Gy in 1.8 Gy fractions. Low dose rate tandem and ovoid implants delivered a cumulative dose to point A of at least
80 Gy, followed by sidewall boost where appropritate.
Regional whole pelvis hyperthermia was given on a weekly basis approximately 30 minutes following external beam radiation
using a BSD 2000 ™ annular phased array.
Results: Clinical response: The median followup for all patients is 18 months (range 5 – 27). Both patients treated for recurrent
disease had local and systemic progression, and died of disease within 6 months. For the remaining 10 patients treated at the
time of initial diagnosis, 10/10 had a clinical complete response. All patients have durable local control. Two patients failed
outside the pelvis, one with pulmonary metastasis and one with isolated para aortic nodal (PA) involvement. The patient with
PA nodal involvement originally had a 6 cm stage IIIB tumor and failed 10 months post CDDP, HT, and RT. She was salvaged
with additional CDDP and PA nodal RT and remains NED at 20 months. Acute toxicity: All patients completed therapy without
requiring treatment breaks. Toxicities included grade 1 – 2 nausea, diarrhea, myelosupression, fatigue, and skin irritation. No
significant toxicities were related to hyperthermia. All acute toxicities were managed on an outpatient basis with standard
supportive care. Late toxicity: One patient with a IIB 8 cm tumor developed a rectovaginal fistula which required a diverting
colostomy 10 months after completing therapy. Exam under anesthesia and multiple biopsies were negative for tumor. The
patient is now 14 months post colostomy and remains without evidence of disease.
64               I. J. Radiation Oncology   ● Biology ● Physics           Volume 51, Number 3, Supplement 1, 2001

     Conclusion: This small phase I/II series is the first to demonstrate that trimodality therapy with CDDP, HT, and RT is feasible,
     well tolerated, and shows clinical promise. Compelling results for locally advanced cervix cancer from five phase III studies
     demonstrate a benefit to adding CDDP based chemotherapy to radiation therapy. A recently published phase III trial by the
     Dutch hyperthermia group demonstrates a survival and local control benefit to the addition of HT to radiation therapy. The
     addition of hyperthermia to chemoradiotherapy may represent a new strategy for combined modality therapy of advanced cervix
     cancer, and deserves significant multi institutional and international collaborative efforts.

     112      Chemoradiation and Radiation Therapy in Cervical Cancer - A Meta-Analysis of Randomized Controlled

     M.C. Cruz
     Division of Therapeutic & Radiologic Oncology, St. Luke’s Medical Center, Quezon City, Philippines

     Purpose: To provide a quantitative estimate of the effects of chemoradiation and radiation therapy alone in patients with cerical
     cancer (locally advanced and bulky disease) in terms of improvement in overall survival, progression free survival, degree of
     toxicity and recurrences.
     Materials and Methods: A quantitative meta-analysis based on updated data. A search from Medline, Cochrane library,
     textbooks and cross-references was carried out and limiting the search to randomized controlled studies. The clinical question:
     Dose chemoradiation (intervention) improves overall survival (outcome) in patients with locally advanced and bulky disease
     cervical cancer (patients)was formulated. Survival time, progression free survival, degree of toxicity, and recurrences were
     defined. Absolute risk reduction (ARR), Number needed to Treat and Odds ration with 95% CI were computed.
     Results: Out of 12 randomized controlled trials and 1 meta-analysis, only 5 were included. A total of 1314 patients were
     considered in the analysis. For survival outcome, the absolute risk reduction was 6% from CT plus RT compared with RT alone,
     needing only 16 patients to treat to prevent 1 from dying of the disease. Progression free survival showed an ARR of 13% for
     CT      RT vs RT alone, needing only 7 patients to treat to prevent from having disease progression. Acute hematologic,
     gastronintestinal and cutaneous toxicity were pronounced for CT RT group, however, these were only transient. Late toxicity
     showed no difference. Recurrences were more common in the RT alone arm. Odds ratio for death is 0.56(95% Cl 0.43, 0.73
     p 0.05), Progression of disease is 0.47(95% Cl 0.36, 0.61 p 0.05), overall acute toxicity is 7.11(95% Cl 5.91, 8.55 p 0.05)
     late toxicity is 0.88(95% Cl 0.55, 1.41 p not significant), pelvic recurrences is 0.69 (95% Cl 0.46, 1.03 p not significant),
     loco-distant recurences is 0.48 (95% Cl 0.26, 0.88 p 0.05) and distant recurrence is 0.49 (95% Cl 0.31, 0.78 p 0.05).
     Conclusion: Quantitative analysis of 5 randomized controlled trials provides us with strong and remarkable evidence that
     combination chemotherapy and complete irradiation (EBRT              brachytherapy) significantly improves overall survival and
     progression free survival. It significantly decreases recurrences rate. Although there was transient increased in acute side effect,
     late effects were comparable.

     113      The American Brachytherapy Society Recommendations for Low Dose Rate Brachytherapy for Carcinoma
              of the Cervix

     S. Nag, C. Chao, B. Erickson, J. Fowler, N. Gupta, A. Martinez, B. Thomadsen
     Clinical Research Committee, American Brachytherapy Society, Oakbrook, IL

     Purpose: This report presents guidelines for using low dose rate (LDR) brachytherapy in the management of patients with
     cervical cancer.
     Materials and Methods: Members of the American Brachytherapy Society (ABS) with expertise in LDR brachytherapy for
     cervical cancer performed a literature review, supplemented by their clinical experience, to formulate guidelines for LDR
     brachytherapy of cervical cancer.
     Results: The ABS strongly recommends that radiation treatment for cervical carcinoma (with or without chemotherapy) should
     include brachytherapy as a component. Precise applicator placement is essential for improved local control and reduced
     morbidity. The outcome of brachytherapy depends, in part, on the skill of the brachytherapist. Doses given by EBRT and
     brachytherapy depend upon the initial volume of disease, the ability to displace the bladder and rectum, the degree of tumor
     regression during pelvic irradiation, and institutional practice. The ABS recognizes that intracavitary brachytherapy is the
     standard technique for brachytherapy for cervical carcinoma. Interstitial brachytherapy should be considered for patients with
     disease that cannot be optimally encompassed by intracavitary brachytherapy. The ABS recommends completion of treatment
     within 8 weeks. Prolonging total treatment duration can adversely affect local control and survival. Recommendations are made
     for definitive and post-operative therapy after hysterectomy for intracavitary and interstitial brachytherapy. While recognizing
     that many efficacious LDR dose schedules exist, suggested dose and fractionation schemes for combining the EBRT with LDR
     brachytherapy for each stage of disease are presented. Dose rates of 0.50 - 0.65 Gy/hr are suggested for intracavitary
     brachytherapy. Dose rates are 0.50 - 0.70 Gy/hr to the periphery of the implant are suggested for interstitial implant. Use of
     differential source activity minimizes excessive central dose rates. The dose prescription point (Point A) is defined for
     intracavitary insertions. The ABS recommends reporting the following parameters. For intracavitary insertions: the prescription,
     including the prescribed dose to points A, dose rate, implant duration, radionuclide used, sources’ strengths, and loading pattern;
     the type of applicator used; doses to vaginal dose points Vs & Vd; doses to rectal and bladder points; and dose to the pelvic
     wall, Point PW. For interstitial implants: the prescription, including the prescribed dose, dose rate, implant duration,
     radionuclide used, sources’ strengths, and loading pattern; the type of applicator used; the volume encompassed by the
     prescribed isodose surface; the maximum significant dose; and rectal and bladder doses if assessed. Considerations for future
     image-based dosimetry are also noted. These recommendations are intended only as guidelines. The responsibility for medical
     decisions ultimately rests with the treating radiation oncologist.
     Conclusion: Guidelines are established for LDR brachytherapy for cervical cancer. Practitioners and cooperative groups are
     encouraged to use these guidelines to formulate their treatment and dose reporting policies.

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