Stage IB2-IVA Cervical Cancer Research Articles

Rate of para-aortic lymph node micrometastasis in patients with locally advanced cervical cancer

Objective Patients with micrometastasis to para-aortic lymph nodes may benefit from extended field chemoradiation. To determine the rate of para-aortic node micrometastasis in patients with locally advanced cervical cancer undergoing laparoscopic extraperitoneal para-aortic lymphadenectomy. Methods We prospectively identified consecutive patients diagnosed with stage IB2-IVA biopsy-proven cervical cancer. Eligible patients included those who were candidates for treatment with radiotherapy and concurrent chemotherapy and had no evidence of para-aortic lymphadenopathy (all lymph nodes < 2 cm in diameter) by preoperative computed tomography or magnetic resonance imaging. All patients underwent preoperative positron emission tomography/computed tomography and laparoscopic extraperitoneal para-aortic lymphadenectomy. All lymph nodes were assessed for metastasis by routine hematoxylin–eosin (H&E) staining. Ultrastaging (serial sectioning) and immunohistochemical analysis were performed in H&E-negative specimens. Results Thirteen (22%) of 60 consecutive patients had para-aortic lymph node metastases detected on routine H&E staining. Of the remaining 47 patients, one (2.1%) had evidence of micrometastasis, which was detected by ultrastaging. This patient completed whole pelvic radiotherapy and chemotherapy but had a recurrence 27 months after completion of therapy. Conclusions The rate of para-aortic node micrometastasis in patients with locally advanced cervical cancer is low. The role of routine ultrastaging and immunohistochemical analysis in such patients remains uncertain. Future studies are needed to determine the clinical impact of para-aortic node micrometastasis in patients with locally advanced cervical cancer.

MO-E-BRB-04: Combining Model Parameters - Radiosensitivity and Dead-Cell Resolving Time to Predict Outcome of Radiation Therapy for Cervical Cancer

Purpose: Individual kinetic modeling parameters can provide important information on predicting clinical outcome in tumors. The combination of model parameters might be very useful in enhancing outcome prediction. This study was to investigate combined effects of radiaosensitivity and dead-cell resolving time on outcome prediction in cervical cancer during radiation therapy (RT). Methods and Materials: Four sequential MRI scans were performed at pre-RT, every 2–2.5 weeks during RT and post-RT for 80 patients with Stage IB2-IVA cervical cancer. Data of 3D-volumetric tumor regression were analyzed. A kinetic model incorporating effects of radiation cell killing, tumor repopulation, and resolution of dead/inactivated cells, was used to fit the tumor regression data for individual patients, resulting in two model parameters: the radiation sensitivity after 2 Gy (S2) and the half-time of dead-tumor-cell resolving (T1/2). Patients were stratified into four subgroups according to optimal cut-points of S2 and T1/2: low S2/loW T1/2 (low-low), high S2/low T1/2 (high-low), low S2/high T1/2 (low-high), and high S2/high T1/2 (high-high). These combined parameters were correlated with long-term clinical outcome (follow-up time: 6.2 years, range: 0.2–9.4 years). Results: In multivariate analysis incorporating stage, tumor size, combined S2 and T1/2, the low-low and high-low parameters were independent prognostic factors for local recurrence and disease-specific survival (hazard ratio [HR]=0.026, 95% confidence interval [CI], 0.003–0.199, p<.001; HR=0.102, 95% CI, 0.018–0.573, p=0.01, respectively). The 6-year local tumor control rate was 100%, 84.2%, 57.1%, and 9.1% for the low-low, high-low, low-high, and high-high subgroups (p<0.001), respectively. Similarly the 6-year disease-free survival was 79.1%, 73.7%,42.9% and 18.2% for the low-low, high-low, low-high, and high-high subgroups (p<0.001), respectively. Conclusion: The combination of kinetic model parameters significantly strengthened the predictive power for therapy outcome. This method has potential value to impact personalized risk-adapted treatment strategy in cervix cancer patient.

Translating Response During Therapy into Ultimate Treatment Outcome: A Personalized 4-Dimensional MRI Tumor Volumetric Regression Approach in Cervical Cancer

To assess individual volumetric tumor regression pattern in cervical cancer during therapy using serial four-dimensional MRI and to define the regression parameters' prognostic value validated with local control and survival correlation. One hundred and fifteen patients with Stage IB(2)-IVA cervical cancer treated with radiation therapy (RT) underwent serial MRI before (MRI 1) and during RT, at 2-2.5 weeks (MRI 2, at 20-25 Gy), and at 4-5 weeks (MRI 3, at 40-50 Gy). Eighty patients had a fourth MRI 1-2 months post-RT. Mean follow-up was 5.3 years. Tumor volume was measured by MRI-based three-dimensional volumetry, and plotted as dose(time)/volume regression curves. Volume regression parameters were correlated with local control, disease-specific, and overall survival. Residual tumor volume, slope, and area under the regression curve correlated significantly with local control and survival. Residual volumes >or=20% at 40-50 Gy were independently associated with inferior 5-year local control (53% vs. 97%, p <0.001) and disease-specific survival rates (50% vs. 72%, p = 0.009) than smaller volumes. Patients with post-RT residual volumes >or=10% had 0% local control and 17% disease-specific survival, compared with 91% and 72% for <10% volume (p <0.001). Using more accurate four-dimensional volumetric regression analysis, tumor response can now be directly translated into individual patients' outcome for clinical application. Our results define two temporal thresholds critically influencing local control and survival. In patients with >or=20% residual volume at 40-50 Gy and >or=10% post-RT, the risk for local failure and death are so high that aggressive intervention may be warranted.

Additional value of MR/PET fusion compared with PET/CT in the detection of lymph node metastases in cervical cancer patients

We evaluated the additional diagnostic value of magnetic resonance/positron emission tomography (MR/PET) fusion in the detection of metastatic lymph nodes in cervical cancer patients. Seventy nine patients with FIGO stage IB-IVA cervical cancer who had undergone both magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) before lymphadenectomy were included in this study. Image analysis was first performed with PET/CT images only. A second analysis was then performed with MR/PET fused images that focused on the additional information obtained from the MR images. Lymphadenectomy involved removing all visible lymph nodes in the surgical field. To enable nodal group-specific comparisons, para-aortic and pelvic lymph nodes were divided into seven nodal groups: para-aortic, both common iliac, both external iliac and both internal iliac/obturator areas. Histopathological evaluation of lymph nodes has been the diagnostic standard. The value of the additional information from the MR images was evaluated by means of receiver operating characteristic (ROC) analysis. Fused MR/PET rendered readers to detect six more metastatic lymph node groups. The sensitivity and specificity of PET/CT and fused MR/PET were 44.1%, 93.9% and 54.2%, 92.7% respectively. The ROC analysis demonstrated a higher diagnostic performance of fused MR/PET compared to PET/CT alone for detecting lymph node metastases ( p = 0.0259). The findings of this study demonstrate the additional diagnostic value of fused MR/PET images compared with PET/CT in the detection of metastatic lymph nodes in patients with uterine cervical cancer.

Acute toxicity of cyclooxygenase-2 inhibitor rofecoxib as a radiosensitizer for concurrent chemoradiation in the treatment of uterine cervical cancer

To evaluate the acute toxicity of rofecoxib during concurrent use with cisplatin-based chemoradiotherapy (CCRT) in patients with cervical cancer. We evaluated 67 FIGO stage IB2-IVA cervical cancer patients treated with CCRT between June 2002 and July 2004. The study group included patients who received rofecoxib (N=30) and the control group included patients who received CCRT only (N=37). The patients' medical records were retrospectively reviewed for patient characteristics, toxicity related to CCRT and treatment results. There were no significant differences in toxicity between the two groups. The most common acute grade 3/4 toxicity was neutropenia (13.3% in the study group and 21.6% in the control group). Grade 3/4 late toxicity was observed in 2 (6.6%) patients in the study group and 3 (8.1%) in the control group. There was no treatment-related deaths in either group. Six (20.0%) patients in the study group had treatment failure. In the control group, 6 (16.2%) patients experienced treatment failure. Progression-free and overall survival was 55.8+/-4.2 and 59.0+/-2.8 months, respectively, in the study group, and 69.7+/-4.3 and 71.6+/-3.6 months, respectively, in the control group. There were no differences in progression-free and overall survival between the 2 groups. Our data indicate that rofecoxib, at a dose of 25 mg twice daily, has acceptable acute toxicity as a radiosensitizer during CCRT. Although rofecoxib was not efficacious as a radiosensitizer in the present study, the benefit of rofecoxib as a radiosensitizer should be further evaluated in a prospective study.

Optimization of Pulsed Dose Rate Intra-uterine Brachytherapy for Cervix Cancer: A Comparison of Target Volume Doses

Optimization of Pulsed Dose Rate Intra-uterine Brachytherapy for Cervix Cancer: A Comparison of Target Volume Doses

Risk Stratification for Failure in Patients with Advanced Cervical Cancer after Concurrent Chemoradiotherapy: Another Way to Optimise Treatment Results

Aims To identify risk factors for disease-free survival (DFS) and para-aortic lymph node (PALN) metastasis in advanced cervical cancer patients after concurrent chemoradiotherapy (CCRT) using risk stratification. Materials and methods In total, 148 patients with stage IB2–IVA cervical cancer without PALN metastasis treated with a full course of CCRT were included for analysis. Radiotherapy consisted of external beam irradiation followed by four courses of high-dose rate intracavitary brachytherapy using 6.0 Gy to point A. Chemotherapy consisted of weekly cisplatin at a dose of 40 mg/m 2 for a planned six cycles. Cox's proportional hazards model was used for risk stratification for DFS and PALN relapse-free survival. Results Patients were divided into low- and high-risk groups. The low-risk group was composed of patients with stage IB–IIB disease without enlarged pelvic nodes, whereas the high-risk group was comprised of patients with stage IB2–IIB tumours with enlarged nodes or those with stage III–IVA disease. The 4-year DFS for the low- and high-risk groups was 83 and 52%, respectively ( P = 0.0001, relative risk 4.51, 95% confidence interval 1.3–10.7), whereas the 4-year PALN metastasis-free survival for the low- and high-risk groups was 92 and 61%, respectively ( P = 0.0003, relative risk 4.93, 95% confidence interval 1.2–12.5). Conclusion The risk of failure in advanced cervical cancer patients treated in the CCRT era can be predicted. For patients with high risk of PALN relapse, this study can provide patient selection criteria when considering prophylactic PALN irradiation.

Inter- and Intrafractional Tumor and Organ Movement in Patients With Cervical Cancer Undergoing Radiotherapy: A Cinematic-MRI Point-of-Interest Study

Internal tumor and organ movement is important when considering intensity-modulated radiotherapy for patients with cancer of the cervix because of the tight margins and steep dose gradients. In this study, the internal movement of the tumor, cervix, and uterus were examined using serial cinematic magnetic resonance imaging scans and point-of-interest analysis. Twenty patients with Stage IB-IVA cervical cancer underwent pelvic magnetic resonance imaging before treatment and then weekly during external beam radiotherapy. In each 30-min session, sequential T(2)-sagittal magnetic resonance imaging scans were obtained. The points of interest (cervical os, uterine canal, and uterine fundus) were traced on each image frame, allowing the craniocaudal and anteroposterior displacements to be measured. The mean displacements and trends were analyzed using mixed linear models. Prediction intervals were calculated to determine the internal target margins. Large interscan motion was found for all three points of interest that was only partially explained by the variations in bladder and rectal filling. The intrascan motion was much smaller. Both inter- and intrascan motion was greatest at the fundus of the uterus, less along the canal, and least at the cervical os. The isotropic internal target margins required to encompass 90% of the interscan motion were 4 cm at the fundus and 1.5 cm at the os. In contrast, smaller margins of 1 cm and 0.45 cm, respectively, were adequate to encompass the intrascan motion alone. Daily soft-tissue imaging with correction for interfractional motion or adaptive replanning will be important if the benefits of intensity-modulated radiotherapy are to be maximized in women with cervical cancer.

Weekly gemcitabine and cisplatin concurrent with pelvic irradiation for primary therapy of cervical cancer: report of the first seven cases in Thai women

The aim of this study was to evaluate the compliance, response, and side effects of weekly gemcitabine (125 mg/m(2)) given concomitantly with standard weekly cisplatin (40 mg/m(2)) and pelvic radiotherapy for primary treatment of cervical cancer stage IB2-IVA in the first seven Thai cases. Weekly gemcitabine at a dose of 125 mg/m(2) was given concomitantly with cisplatin at 40 mg/m(2) for six cycles with concurrent radiotherapy in primary therapy of stage IB2-IVA cervical cancer. Radiation consisted of 5000 cGy in 25 daily fractions combined with brachytherapy to take point A to about 8600 cGy. Using weekly gemcitabine at a dose of 125 mg/m(2) with cisplatin at a dose of 40 mg/m(2), five of seven patients demonstrated a dose-limiting toxicity (DLT). DLTs consisted of nephrotoxicity in three cases and bone marrow suppression in two cases. Only one of seven patients could go through six cycles. All 5 living patients had a clinically complete response. Weekly gemcitabine at a dose of 125 mg/m(2) with cisplatin at a dose of 40 mg/m(2) given concurrently with primary pelvic radiotherapy resulted in an excellent response but unacceptable toxicities for Thai women. The trial protocol was changed by reducing the cisplatin dosage to 20 mg/m(2).

The comparison of accuracy between PET and PET/CT for detecting lymph node metastasis in cervical cancer: Prospective surgicopathologic study

5587 Background: Previosly, we reported the accuracy of positron emission tomography with 2-[fluorine18] fluoro-2-deoxy-D- glucose (FDG-PET) for detecting metastatic lymph node (LN) in cervical cancer (Eur J Cancer 2005: 41; 2086–92). The aim of this prospective study was to evaluate the accuracy of PET/CT for detecting lymph node metastasis in cervical cancer and to compare the accuracy between PET and PET/CT. Methods: From May 2002 to Jul 2006, 86 patients with untreated stage IB-IVA cervical cancer were enrolled. All patients underwent pretreatment clinical staging including PET (May 2002-Aug 2003, 54 patients) or PET/CT (Jan 2004-Jul 2006, 32 patients) followed by surgical staging including systematic pelvic and paraaortic lymph node (PLN and PALN) dissection. To enable region specific comparisons, PALN and PLN were divided into eight regions: both PALN, both common iliac areas, both external iliac areas, and both internal iliac/obturator areas. Each lymph node was sliced at 2-mm intervals perpendicular to the greatest dimension to maximize the likelihood of detecting micrometastases. All metastatic tumor size in each involved lymph node was measured. Histopathologic evaluation of lymph nodes was the diagnostic standard. The study protocol was approved by Institutioal Review Board, and a written informed consent was obtained. Results: A total of 688 LN regions were evaluated. The sensitivity, specificity, positive predictive value, and negative predictive value of PET and PET/CT are shown in Table 1 . As the metastatic tumor size increased, the sensitivity of PET and PET/CT was improved. Although there were no differences in sensitivity for detecting large sized (&gt; 5mm or 10mm) metastatic tumor, PET/CT was more sensitive than PET for all pathologically proven LN metastasis which included small sized (&lt; 5mm) metastatic tumor. Conclusions: PET/CT was more sensitive than PET for detecting small sized (&lt;5mm) lymph node metastasis in cervical cancer. [Table: see text] No significant financial relationships to disclose.

Equivalent survival in patients with advanced stage IB–II and III–IVA cervical cancer treated by adjuvant surgery following chemoradiotherapy

Objectives To evaluate survival in patients with advanced cervical cancer who underwent surgery after concurrent chemoradiotherapy. Methods One hundred and forty-four patients with biopsy-proven stage IB–IVA cervical cancer underwent adjuvant surgery after concurrent chemoradiotherapy. Surgical resection was classified as curative (no evidence of remaining disease after surgery) or palliative (remaining disease after surgery). Endpoints were pelvic control, overall survival (OS) and disease-free survival (DFS) at 5 and 10 years. Analysis included tumour FIGO stage, type of surgery (curative versus palliative), pelvic control, response to chemoradiotherapy and lymphatic status. Results Tumour FIGO stages were IB–II in 91 cases and III–IVA in 53 cases. Surgery was curative in 127 cases. Pelvic control was achieved in 114 patients and was equivalent in stage IB–II and III–IVA patients. So far, 60 patients have died. The 5-year OS and DFS rates were, respectively, 57.6% [95% CI: 49.1–67.5] and 65% [95% CI: 56.2–75]. OS was significantly affected by the type of surgery ( p < 2.10 −16), the presence of tumoural residue ( p = 0.002) and the pelvic lymphatic status ( p < 0.001). DFS was affected by the pelvic ( p = 0.02) and para-aortic lymphatic status ( p = 0.009). No significant difference was observed between OS and DFS in stage IB–II and III–IVA patients, whereas a macroscopic tumoural residue was observed in, respectively, 30.9 and 52.2% of cases ( p = 0.022). Conclusion Survival rates were equivalent between patients with IB–II and III–IVA cervical cancer, suggesting that adjuvant surgery following chemoradiotherapy may improve local control.

Early Clinical Outcome With Concurrent Chemotherapy and Extended-Field, Intensity-Modulated Radiotherapy for Cervical Cancer

To assess the early clinical outcomes with concurrent cisplatin and extended-field intensity-modulated radiotherapy (EF-IMRT) for carcinoma of the cervix. Thirty-six patients with Stage IB2-IVA cervical cancer treated with EF-IMRT were evaluated. The pelvic lymph nodes were involved in 19 patients, and of these 19 patients, 10 also had para-aortic nodal disease. The treatment volume included the cervix, uterus, parametria, presacral space, upper vagina, and pelvic, common iliac, and para-aortic nodes to the superior border of L1. Patients were assessed for acute toxicities according to the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0. All late toxicities were scored with the Radiation Therapy Oncology Group late toxicity score. All patients completed the prescribed course of EF-IMRT. All but 2 patients received brachytherapy. Median length of treatment was 53 days. The median follow-up was 18 months. Acute Grade > or = 3 gastrointestinal, genitourinary, and myelotoxicity were seen in 1, 1, and 10 patients, respectively. Thirty-four patients had complete response to treatment. Of these 34 patients, 11 developed recurrences. The first site of recurrence was in-field in 2 patients (pelvis in 1, pelvis and para-aortic in 1) and distant in 9 patients. The 2-year actuarial locoregional control, disease-free survival, overall survival, and Grade > or = 3 toxicity rates for the entire cohort were 80%, 51%, 65%, and 10%, respectively. Extended-field IMRT with concurrent chemotherapy was tolerated well, with acceptable acute and early late toxicities. The locoregional control rate was good, with distant metastases being the predominant mode of failure. We are continuing to accrue a larger number of patients and longer follow-up data to further extend our initial observations with this approach.

Contribution of surgery in patients with bulky residual disease after chemoradiation for advanced cervical carcinoma

Aim To report the outcome of 30 patients who underwent surgery after concomitant chemoradiation for locally advanced cervical cancer with residual disease ≥2 cm. Methods From 1988 to 2004, 143 patients with FIGO stage IB2–IVA cervical cancer underwent surgery after concurrent chemoradiotherapy. Among them, 30 had a residual cervical tumour ≥2 cm prior to surgery. Surgery consisted in a simple or radical hysterectomy ( n = 15) or in a pelvic exenteration ( n = 15). Endpoints were recurrence and distant metastasis rates, overall survival (OS) and disease-free survival (DFS) at 3 and 5 years. Analysis included FIGO stage, response to chemoradiation, para-aortic lymphatic status or type of surgery: palliative (remaining disease after surgery) or curative (no evidence of remaining disease after surgery). Results Surgery has been only palliative in 11 cases. Pelvic recurrences occurred in 8 patients after a median interval of 8.8 months. Distant metastases occurred in 8 patients after a median interval of 13 months. So far, 16 patients have died (53.3%). The 3-year and 5-year OS rates are 64.9% and 55.6%, respectively, for the 19 patients who had a curative surgery. The DFS rate is 50.8% at 3 and 5 years in this latter group. Overall 12 patients (40%) are alive and free of disease after a median follow-up of 32.5 months. Conclusions Adjuvant surgery may improve the outcome of patients with bulky residual tumour after chemoradiation for locally advanced cervical cancer, allowing a 5-year OS of 55.6% after curative intervention.

Dosimetric factors predicting severe radiation-induced bowel complications in patients with cervical cancer: combined effect of external parametrial dose and cumulative rectal dose

ObjectiveThe purpose of this study was to analyze dosimetric factors of radiation-induced severe bowel complications among patients with cervical cancer. MethodsWe reviewed 297 patients of stage IB–IVA cervical cancer managed by curative-intent radiotherapy from May 1993 through December 1997. Whole-pelvic irradiation of external beam radiation therapy (EBRT) (34.2–48.6 Gy/19–27 fractions) was delivered to all patients. Two hundred and three patients received additional bilateral parametrial boost (3.6–18 Gy/2–10 fractions). High dose-rate (HDR) intracavitary brachytherapy (ICBT), 16–24 Gy/5 fractions to Point A, was given after external irradiation. Cumulative rectal biologically effective dose (CRBED) at rectal reference point was determined by summation of EBRT and ICBT component. ResultsThe 5-year incidences of Grade 3–4 enterocolitis and proctitis were 10% and 7%, respectively. Both complications were associated with external parametrial dose (PMD) and CRBED. Interaction of CRBED and PMD was noted in multivariate analysis of enterocolitis (P < 0.001) and proctitis (P < 0.001). In CRBED ≥ 100 Gy3 group, PMD was an independent factor in enterocolitis (P = 0.010) and proctitis (P = 0.039). In PMD ≥ 54 Gy group, CRBED was an independent factor in enterocolitis (P = 0.003) and proctitis (P = 0.036). Patients with both PMD ≥ 54 Gy and CRBED ≥ 100 Gy3 had higher incidence of 5-year enterocolitis (26%) (P < 0.001) and proctitis (17%) (P < 0.001) than other dose groups. ConclusionRadiation-induced severe bowel complications are association on both high PMD and high CRBED. We do not suggest both external PMD ≥ 54 Gy and CRBED ≥ 100 Gy3 for treatment of cervical cancer due to unacceptably high incidence of severe bowel complications.

Randomized double-blind placebo-controlled trial of balsalazide in the prevention of acute radiation enteritis as a consequence of pelvic radiotherapy

Acute radiation enteritis (ARE) is a common complication in pelvic radiotherapy (RT) patients. Manifested as diarrhea, tenesmus, abdominopelvic pain, and peri-rectal discomfort, ARE results largely from irritation of the sigmoid colon and rectum by RT. Even with highly conformal techniques, sparing these structures may be difficult. Thus, interventions to limit ARE have broad applicability and potential to enhance patients’ quality of life. 5-amino-salicylates (5-ASA) are traditionally used to treat inflammatory bowel disease. All but one prior attempt at using 5-ASA to prevent ARE have failed. We sought to evaluate balsalazide (BSZ), a new 5-ASA agent, for its potential to prevent or limit ARE in patients receiving RT for prostate or cervical cancer. BSZ has unique advantages: its delivery system yields higher concentrations of active 5-ASA in the distal colon and rectum than other agents, and it lacks the antigenic sulfa moiety present in sulfasalazine, the only other 5-ASA with demonstrated benefit in this setting. Thus, we considered it an ideal candidate for preventing or limiting ARE. Informed consent was obtained prior to entry into this IRB-approved study. The accrual goal was 100 patients, 50 in each arm. Eligible patients included those treated for FIGO stage IB2-IVA cervical cancer, AJCC Stage T1-3 M0 prostate cancer, or biochemical failure after prostatectomy. RT was delivered in a 4-field technique to at least 45 Gy, and tumor dose was at least 64 Gy for prostate patients or 75 Gy for cervical patients. Brachytherapy boost was permitted. Other criteria were age 18 years or older and KPS above 70% Patients were given 2250 mg of BSZ or an identical-appearing placebo twice daily beginning 5 days prior to RT, and continuing for 2 weeks after completion. Toxicities were graded weekly according to NCI Common Toxicity Criteria for each of the following: proctitis, diarrhea, dysuria, weight loss, fatigue, nausea, and vomiting. A symptom index was formulated for each toxicity consisting of the toxicity’s numeric grade multiplied by the number of days it was experienced, and summed for each grade. Thus, a patient with 7 days of grade 1 proctitis, 14 days of grade 2 proctitis, and 7 days of grade 3 proctitis [(1*7)+(2*14)+(3*7)] would have a proctitis index of 56. A higher index indicates worse toxicity. Except nausea/vomiting, seen in 2 patients on BSZ and 1 on placebo, all toxicities were appreciably lower in patients taking BSZ. Proctitis was prevented most effectively, with a mean index of 35 in BSZ patients vs. 77 in placebo patients (p = 0.04). No patient on BSZ experienced grade 4 diarrhea, while 2 placebo patients did. Average weight loss in placebo patients was greater than 3 lbs., whereas average BSZ patients gained weight. Fatigue index in BSZ patients was 20, while placebo patients averaged 49. Unexpectedly, dysuria was appreciably lower in BSZ patients as well. BSZ is a new-generation 5-ASA drug with significant potential to prevent or reduce symptoms of ARE in patients undergoing pelvic RT. We feel that our pilot study justifies the formation of a cooperative group trial to assess its efficacy in a multi-institutional setting.

High External Parametrial Dose Can Increase the Probability of Radiation Proctitis in Patients with Uterine Cervix Cancer

Objective. The aim of this study was to evaluate the relationship between external parametrial dose and radiation proctitis after external irradiation and high-dose-rate intracavitary (HDR-IC) brachytherapy among patients with cervical cancer.Methods. From May 1993 through December 1996, 191 patients with stage IB–IVA cervical cancer were managed by curative-intent radiotherapy. External irradiation to the whole pelvis (44–45 Gy/ 22–25 fractions) was delivered to all patients initially. One hundred twenty-seven patients received additional bilateral parametrial and sidewall boost (5.4–14.4 Gy/ 3–8 fractions) with 4-cm midline shielding. HDR-IC brachytherapy, 19.2–24 Gy/ 5 fractions to Point A, was given after external irradiation. Patients receiving an external dose of 44–45, 50–54, and >54 Gy were categorized as no parametrial boost (NPMB), low parametrial boost (LPMB), and high parametrial boost (HPMB) group, respectively. The actuarial proctitis rate was compared among the three groups.Results. Three-year overall and Grade 2–4 proctitis rates were 30 and 15%, respectively. Overall proctitis rates were 12, 34, and 51% in the NPMB, LPMB, and HPMB groups (P < 0.0001), respectively. Grade 2–4 proctitis rates were 5, 17, and 27% in the NPMB, LPMB, and HPMB groups (P = 0.0022), respectively. In multivariate analysis of overall and Grade 2–4 radiation proctitis, external parametrial dose was the only independent prognostic factor (P = 0.0002 and 0.0030, respectively).Conclusion. Regardless of central shielding after 44–45 Gy whole pelvis irradiation, more patients with high external parametrial dose developed radiation proctitis. Incomplete midline shielding of the upper rectum may be the cause. Diminishing the external beam doses further may decrease rectal complications.