Radiochemotherapy for patients with locally advanced cervical cancer: early results

PURPOSE: Radiotherapy is the standard treatment for locally advanced cervical cancer. Recent results of the prospective randomized trials have shown an overall survival and local control advantage for cisplatin-based therapy given concurrently with radiation therapy. Thirty-nine patients who received concurrent chemoradiation between October 1999 and December 2000 were evaluated for treatment response, local control and toxicity. MATERIALS AND METHODS: Thirty-nine patients with Stage IB through IVA cervical carcinoma received weekly cisplatin (40 mg/m2) concurrent with radiotherapy. Thirty-two patients received both external and intracavitary radiotherapy and seven patients received only external radiotherapy because of insufficient tumor response for intracavitary application. Total external radiotherapy dose was 64.8 Gy with 1.8 Gy daily fractions in patients who received only external radiotherapy. Midline shielding was performed at 50.4 Gy in patients who were going to receive brachytherapy and the total external radiotherapy dose was 54-59.4 Gy. Brachytherapy was performed with a Rotterdam applicator via the microSelectron HDR machine. A total dose of 8.5-18 Gy was applied to point A. RESULTS: Median age was 55. Distribution by stages were as follows: Stage IB 5.1%, IIA 28.2%, IIB 43.6%, IIIA 7.7%, IIIB 12.8% and IVA 2.6%. Histologically 33 (84.6%) were epidermoid carcinoma, one was adenocarcinoma, two were undifferentiated carcinoma, one was malignant epithelial tumor. In two patients histological type could not be specified. The median duration of follow-up was 20 months. Four patients had local recurrence and three developed distant metastases. Thirty patients (76.9%) had complete response, eight had (20.5%) partial response and one had (2.6%) stable disease. During or after radiochemotherapy 46.2% of the patients developed toxicity due to chemotherapy. Early and late radiation morbidity rates were 66.7% and 71.8%, respectively. No grade III-IV toxicity was observed. CONCLUSION: Concurrent chemoradiation for locally advanced cervical cancer is the treatment of choice in suitable patients providing high response rates with acceptable toxicity.     

Early clinical outcomes of 3D-conformal radiotherapy using accelerated hyperfractionation without intracavitary brachytherapy for cervical cancer

PURPOSE/OBJECTIVE: To evaluate the outcome of cervical cancer patients unable to undergo conventional intracavitary brachytherapy (ICBT) treated with 3D-conformal radiotherapy (3DCRT) alone using accelerated hyperfractionation (AHF). METHODS AND MATERIALS: We reviewed the records of 7 patients who had received definitive radiotherapy with 3DCRT alone using AHF for cervical cancer between 2002 and 2005. FIGO stage was IB (1), IIB (2), IIIA (1), IIIB (2), and IVA (1). The reason we did not perform ICBT was due to patient refusal. In 1 patient with stage IB, a total dose of 65.4 Gy was delivered by local irradiation (LI) only. In 1 patient with stage IIIA, a total dose of 60 Gy was delivered by LI only. In 5 patients with Stage IIB-IV, a median total dose of 70.8 Gy was delivered by combination of whole pelvic irradiation (median dose of 45 Gy) with LI. Median overall treatment time was 42 days. RESULTS: Median follow-up for survival patients was 17 months. Out of 7 patients, 6 patients had CR and 1 patient had PR. The response rate was 100%. The 2-year local control rate was 85.7%. Of these patients, 5 are alive without disease and 1 is alive with lung metastasis. CONCLUSIONS: Our outcomes suggest that 3DCRT using AHF may be a promising as a definitive treatment for cervical cancer when ICBT is not able to be performed.     

Long-term results of high-dose rate brachytherapy in cervix cancer using a small number of fractions

OBJECTIVES: To evaluate the long-term treatment outcome of patients with carcinoma of the cervix treated with high dose rate brachytherapy (HDRB) using a small number of fractions. METHODS: Between 1984 and 1997, 282 patients with cervix cancer (stages IB to IVA) were treated with external beam radiotherapy to the whole pelvis (median dose of 45 Gy) and HDRB (median dose of 24 Gy at point A in 3 insertions given weekly). Endpoints assessed were survival, patterns of failure and complications. Multivariate analysis was performed to identify variables predictive for overall survival and local control. Variables investigated were stage, age, overall duration of treatment, HDRB scheduling and total dose to point A. RESULTS: At a median follow-up of 86.3 months for patients at risk, the 5-, 10- and 15-year overall survival rates are 57%, 52% and 47%, respectively. On multivariate analysis, only stage and age correlated with improved survival. Treatment duration beyond 47 days was associated with poorer overall survival, although it did not reach statistical significance (P = 0.10). Brachytherapy scheduling and BED to point A had no impact on overall survival. Stage and age significantly correlated with pelvic disease control. Duration of therapy, scheduling of the brachytherapy and BED at point A were not individual predictors for overall local control. Overall, gastrointestinal and genitourinary actuarial complication rates were 15% and 8%, respectively. CONCLUSIONS: In our experience, HDRB using 3 insertions is well tolerated and the results are comparable to HDRB using larger number of fractions and to low dose rate brachytherapy.     

Phase I clinical trial of weekly paclitaxel, weekly carboplatin, and concurrent radiotherapy for primary cervical cancer

OBJECTIVES: Standard primary treatment for locally advanced cervix cancer is radiation (RT) with concomitant platinum-based chemotherapy (CT). Incomplete local control and the appearance of distant disease herald poor survival and warrant evaluation of new primary strategies. Paclitaxel and carboplatin are active agents in recurrent cervical carcinoma, have potent, synergistic in vitro radiosensitization, and are cytotoxic in weekly schedules. This study was done to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly paclitaxel/carboplatin chemoradiotherapy in locally advanced cervix cancer. METHODS: Women with primary, previously untreated, squamous cell or adenocarcinoma of the cervix, FIGO stage IB(2) to IVA, negative para-aortic lymph nodes, adequate organ function and performance status were eligible. Pelvic RT (45 Gy over 5 weeks--180 cGy/day, four-field) was followed by two brachytherapy applications (Point A low dose rate (LDR): 90 Gy, high dose rate (HDR): 75 Gy). Concurrent weekly CT was paclitaxel 50 mg/m(2) and carboplatin, starting at AUC 1.5 and escalating in three-patient cohorts by AUC 0.5 (Max AUC 3.5). Dose escalation followed a 4-week observation period for toxicity. A grade III-IV toxicity prompted up to three additional patients per dose level. A second event defined DLT. CT was administered concurrently throughout brachytherapy. RESULTS: Fifteen patients were enrolled and treated over four dose levels until DLT was reached. Median age was 44 years (range, 23-70); stages: IB2: 1, IIB: 9, IIIA: 1, IIIB: 4. Median RT treatment time was 61 days (range, 55-79). Fourteen patients received brachytherapy (LDR: 8, HDR: 6), and one received external RT only due to cervical stenosis. The median number of weekly CT cycles was seven (range, 6-7). One CT dose was dropped in one patient for a grade II thrombocytopenia. One grade III ANC was observed at dose level II (AUC 2.0) but not seen in three additional patients. At dose level IV (AUC 3.0), two grade III-IV ANC toxicities were observed in two patients (DLT). Nine patients had grade II anemia. One patient had grade III anemia. Grade III/IV nonhematologic toxicity was rare (1/15 GI-nausea/vomiting, 1/15 pneumonia, 1/15 hypokalemia). The MTD of carboplatin is AUC 2.5 with paclitaxel 50 mg/m(2). Median follow-up is 17 months; three patients have recurred and two have died. The estimated 2-year PFS and OS are 80% and 86%. CONCLUSIONS: Weekly paclitaxel and carboplatin chemoradiation is feasible and active. The MTD for a phase II trial is 50 mg/m(2) and AUC 2.5, respectively.     

Survival following extended field irradiation in carcinoma of cervix metastatic to para-aortic lymph nodes

OBJECTIVE: Our goal was to determine survival after extended-field treatment of para-aortic lymph node (PALN) metastasis. METHODS: Thirty-five patients were treated from 1975-1989 for PALN metastasis. The FIGO stages were IB 10, 2A 3, IIB 9, IIIA 1, IIIB 10, 4A 1, and unstaged 1. The diagnosis in 34 patients was by operative staging and in 1 by CT scan and fine-needle aspiration biopsy. Twelve patients had microscopic PALN metastasis (PALN1) and 23 had grossly enlarged lymph nodes (PALN2). Thirty-four patients had extended-field radiotherapy (RT) plus brachytherapy or pelvic boost. Kaplan-Meier estimates were computer calculated for the entire population. Late radiation morbidity was classified by RTOG/EORTC criteria. RESULTS: The 5-year overall survival rate was approximately 29%. Four patients (3 stage IB, 1 stage IIIA) survived without recurrence. All four had extended field RT. The 5-year survival rate was 41.7% for PALN1 cases and 26.1% for PALN2 cases. Three patients (8.6%) had Grade 4 morbidity. CONCLUSIONS: PALN metastasis in stage IB is curable in approximately 30% of cases. The management approach in this series in stage IB was as follows: If PALN metastasis was identified at exploration for radical hysterectomy, the procedure was aborted and extended-field RT administered. In stages IIB through IVA, operative staging or CT scanning with FNA biopsy of suspicious PALN was performed. If PALN metastasis was confirmed, extended-field RT was administered. A 35% 5-year survival rate was observed in the advanced group. The value of chemotherapy for PALN metastasis remains to be defined but results from clinical trials suggest that cisplatin-based chemotherapy may be beneficial.     

Carcinoma of the cervix in young females (35 years, and younger)

This retrospective study involved 55 patients, 35 years old or less with invasive carcinoma of the cervix. There were 49 squamous carcinomas, 3 adenocarcinomas, and 3 unusual varieties. Thirty-five patients had stage IB disease; 4 had stage IIA disease; 6 had stage IIB disease; 5 had stage IIIB disease, and 3 had stage IV disease. Treatments employed were either radical hysterectomy and node dissection, irradiation, or irradiation followed by radical surgery. Our overall 5-year disease-free survival among young females with stage IB disease was observed to be only 43%; stage IIA only 25%; stage IIB only 17%, and no survivors in more advanced stages.     

Radiation therapy alone in the treatment of carcinoma of the uterine cervix: a 20-year experience

A retrospective analysis is reported on the results of irradiation alone in the treatment of 970 patients with histologically proven invasive carcinoma of the uterine cervix. The development of the radiation therapy techniques, survival, pelvic tumor control, and major sequelae of therapy are described in detail. The tumor-free 5-year survival rate was 100% in 29 patients with stage IA, 85% in 312 cases with stage IB, 70% in 98 patients with stage IIA, 68% in 276 patients with stage IIB, 45% in 237 stage III cases, and one survivor in 18 stage IV patients. No pelvic recurrences or distant metastases were observed in stage IA patients. In stage IB the overall incidence of pelvic recurrences was 7.3%, in stages IIA and IIB 14%, and in stage III 37%. Distant metastases were noted in 13% of the patients with stage IB, 22% of those with stages IIA and IIB, and 32% of patients with stage III tumors. Higher doses of irradiation delivered with intracavitary insertions and extenal beam were correlated with a lower incidence of pelvic recurrences in stages IIA, IIB, and III. However, doses to point A over 7000 cGy did not improve pelvic tumor control in stage IB. Grade 2 treatment sequelae were observed in about 10% of all patients and grade 3 complications in approximately 4% of the patients with stage I and 8% in those with more advanced tumors (IIA and beyond). The need is emphasized to carefully evaluate the dosimetric aspects of new techniques, including phantom studies before they are applied to patients. A close integration of external and intracavitary irradiation will result in better tumor control and fewer complications.     

Intraarterial cisplatin/nedaplatin and intravenous 5-fluorouracil with concurrent radiation therapy for patients with high-risk uterine cervical cancer

OBJECTIVE: The purpose of this study was to determine the effectiveness of the combination of intraarterial and intravenous concurrent chemoradiation therapy (CIAIV-CCRT) for the treatment of high-risk uterine cervical cancer. METHODS: Between January 2000 and November 2004, we reviewed 45 cervical cancer patients treated by CIAIV-CCRT. The numbers of patients with stage IB2, IIA, IIB, IIIA, IIIB, and IVA were 3, 6, 14, 1, 17, and 4, respectively. Patients with stage III and IVA or patients with tumors >3 cm in diameter were enrolled in this study. Two sessions of CCRT were administered every 3 weeks using a combination of 70 mg/m2 x h(-1) cisplatin or 50 mg/m2 x h(-1) nedaplatin via the bilateral uterine artery and 2800 mg/m2 x 96 h(-1) 5-fluorouracil intravenously. Patients concurrently received external beam radiation therapy and brachytherapy. A nonrandomized control group of 47 patients who underwent radiation therapy alone between 1993 and 2000 was used for comparison. RESULTS: Of the 45 patients, 28 (62%) exhibited complete response and 16 (36%) exhibited partial response. One IIIB patient (2%) did not show any response. The 5-year overall survival (OAS) rates in the CCRT group and control group were 80.6% and 54.9%, respectively. With regard to late toxicities, no statistically significant differences were observed between the two groups. In uni- and multivariate analyses, positive pelvic lymph node showed a statistically significant influence on the OAS in the CIAIV-CCRT group (P = 0.049). CONCLUSION: These preliminary results suggest that CIAIV-CCRT can improve the prognosis of patients with high-risk cervical cancer.     

Surgery after concurrent chemoradiotherapy and brachytherapy for the treatment of advanced cervical cancer: morbidity and outcome: results of a multicenter study of the GCCLCC (Groupe des Chirurgiens de Centre de Lutte Contre le Cancer)

OBJECTIVES: To evaluate the morbidity and therapeutic value of surgery after concurrent chemoradiotherapy and brachytherapy in a multicentric series of patients with advanced cervical cancer. METHODS: Patients with stage IB2 to IVA cervical cancer treated with concurrent chemoradiotherapy and pelvic radiotherapy followed by brachytherapy and surgery from seven participating French comprehensive cancer centers were enrolled. The surgical treatment consisted of a hysterectomy, which ranged from radical hysterectomy to anterior pelvic exenteration, and lymph node resection. Acute toxicity, pathological response, overall, and disease-free survival were assessed for each pathological response to therapy. RESULTS: One hundred seventy-five patients were enrolled from September 1987 to June 2002. The median age was 44 years [27;75]. Patients distribution according to clinical classification was as follows: 41 stage IB2, 18 IIA, 77 IIB, 12 IIIA, 14 IIIB, and 13 IVA. Forty-six patients experienced 51 postoperative complications. Thirty-three patients experienced grade 2 morbidity (18.9%, 33/175), among whom 19 experienced urinary complications (57.5%, 19/175). No post treatment mortality was observed. Grade 3 toxicity rate was 6.9% (12/175). Pathological complete response rate was 38% (67/175). After a median follow-up of 36 months, overall survival and disease-free survival were significantly better in patients who had a pathological complete response to therapy than those who achieved a partial pathological response (P < 0.0001). CONCLUSION: Surgery after concurrent chemoradiotherapy and brachytherapy for advanced cervical cancer leads to an acceptable morbidity. Furthermore, surgery allows evaluation of the pathological response to therapy and improves local control in the case of partial pathological response.     

Mature Results of a Phase II Trial of Concomitant Cisplatin/Pelvic Radiotherapy for Locally Advanced Squamous Cell Carcinoma of the Cervix

Purpose:Patients with locally advanced squamous cell carcinoma of the cervix have a poor prognosis when treated by standard ratiotherapy (RT) alone. Factors such as large tumor volume or nodal disease result in pelvic and distant treatment failures. Cisplatin (CDDP), a known radiosensitizer with documented activity in squamous cell carcinomas, was used in a phase II prospective study to evaluate the efficacy of combined chemo/radiotherapy in locally advanced squamous cell carcinomas of the cervix.Method:CDDP was administered (20 mg/m²) daily × 5 at 21-day intervals with concomitant external beam and intracavity RT. Standard RT was delivered at 1.8–2.0 Gy/day, 5 fractions per week for 5 weeks. Intracavitary cesium insertions were planned to treat point A to approximately 80 Gy.Results:Fifty-nine patients were enrolled from March 1986 to July 1990. Four patients were voluntarily withdrawn, leaving 55 patients evaluable for response. Of these, 16 were Stage IB/IIA, 11 were Stage IIB, 24 were Stage III, and 4 were Stage IV. The median age of patients enrolled was 47 years (range 27–79). Median follow-up time was 65 months (range 60–113). Histopathologic confirmation of node status was available in 33 patients, of whom 45.5% (15/33) had nodal metastases. Overall response was 96% (CR = 87%, PR = 9.0%) and 3.6% had progressive disease during treatment. Forty-six patients were evaluable at 5 years for overall and disease-free survival. Calculations were based on Kaplan–Meier product limit estimates. The 5-year survival was 73% for Stage IB/IIA, 60% for Stage IIB, 67% for Stage III, and 25% for Stage IV. The disease-free survival at 5 years was 73% for Stage for IB/IIA, 50% for Stage IIB, 67% for Stage III, and 25% for Stage IV. Hematologic toxicity was severe but tolerable. No treatment-related deaths occurred.Conclusion:Concomitant CDDP/RT is a safe and tolerable method of treating patients with locally advanced squamous cell carcinoma of the cervix. Our data suggest a benefit in both disease-free and 5-year survival, particularly notable among patients with Stage III disease.     

Magnetic resonance imaging-based validation of the 2018 FIGO staging system in patients treated with definitive radiotherapy for locally advanced cervix cancer

ObjectiveTo validate the revised 2018 International Federation of Gynecologic and Obstetrics (FIGO) staging system in patients who underwent diagnostic magnetic resonance imaging (MRI) and radiotherapy (RT) for locally advanced cervix cancer.MethodsWe analyzed 677 patients who were diagnosed with pelvic MRI and treated with definitive (chemo-)RT for locally advanced cervix cancer (stage IB2/IIA2-IVA or N+) between 1992 and 2018. Patients were classified according to 2009 and 2018 FIGO staging, and survival outcomes were compared. We developed a nomogram to improve prediction of progression-free survival (PFS).ResultsPelvic and paraaortic lymph nodes were positive in 331 (48.9%) and 78 (11.5%) patients, respectively. At a median follow-up of 77.9 months, the 5-year PFS was 83.5%, 65.2%, 71.0%, 60.6%, 37.6% and 38.9% for IB, IIA, IIB, IIIA, IIIB and IVA according to FIGO 2009 and 88.9%, 60.0%, 73.8%, 66.7%, 36.3%, 68.9%, 43.6%, and 38.9% for IB, IIA, IIB, IIIA, IIIB, IIIC1, IIIC2, and IVA according to FIGO 2018, respectively. Survival of stage IIIC cervix cancer depended on the local extent of the tumor: the 5-year PFS of T1, T2, and T3 stages were 80.3%, 73.9%, and 45.5% for IIIC1 and 100%, 44.9%, and 23.4% for IIIC2. Histology, tumor size, node metastasis, FIGO 2009, and treatment modality were independent prognostic factors in the Cox regression analysis, and the nomogram incorporating these factors outperformed FIGO 2009 and FIGO 2018 (AUC 0.718 vs. 0.616 vs. 0.594).ConclusionsFIGO 2018 revision was associated with heterogenous outcomes among stage III cervix cancer patients. Our nomogram can assist the FIGO system in predicting PFS after definitive RT.     

High–dose rate brachytherapy in the treatment of carcinoma of uterine cervix: twenty-year experience with cobalt after-loading system

This retrospective analysis aims to report results of patients with cancer of uterine cervix treated with external-beam radiotherapy (EBR) and high-dose rate (HDR) brachytherapy, using manual treatment planning. From 1975 to 1995, 237 patients with FIGO stages IIB-IVA and mean age of 54.31 years were treated. EBR dose to the whole pelvis was 50 Gy in 25 fractions. Brachytherapy with HDR after-loading cobalt source (Cathetron) was performed following EBR completion with a dose of 30 Gy in three weekly fractions of 10 Gy to point A. Survival, local control, and genitourinary and gastrointestinal complications were assessed. In a median follow-up of 60.2 months, the 10-year overall and disease-free survival rate was 62.4%. Local recurrence was seen in 12.2% of patients. Distant metastases to the lymph nodes, peritoneum, lung, liver, and bone occurred in 25.3% of patients. Less than 6% of patients experienced severe genitourinary and/or gastrointestinal toxicity that were relieved by surgical intervention. No treatment-related mortality was seen. This series suggests that 50 Gy to the whole pelvis together with three fractions of 10 Gy to point A with HDR brachytherapy is an effective fractionation schedule in the treatment of locally advanced cancer of cervix. To decrease the complications, newer devices and treatment planning may be beneficial.     

Concurrent radiotherapy with paclitaxel/carboplatin chemotherapy as a definitive treatment for squamous cell carcinoma of the uterine cervix

OBJECTIVES: To evaluate the toxicity and the efficacy of paclitaxel/carboplatin chemoradiotherapy as a definitive treatment for squamous cell cancer of the uterine cervix. METHODS: From March 2000 to January 2004, 33 patients with squamous cell cancer of the uterine cervix were treated with concurrent chemoradiotherapy including 2 cycles of paclitaxel (135 mg/m(2)) and carboplatin (area under the time-concentration curve 4.5 mg min/ml) at 4-week interval. Seven patients received adjuvant chemotherapy with the same chemotherapeutic regimen. All patients received external beam radiotherapy with 41.4-51.4 Gy (median 50.4 Gy) to the whole pelvis. Twenty-eight patients received boost irradiation to the cervix by brachytherapy with 25.6-43.3 Gy (median 34.6 Gy) and 5 patients by external beam radiotherapy with 10.8-14.4 Gy (median 14.4 Gy). RESULTS: A median follow-up period was 27 months (range: 6-53 months). Acute hematological toxicity of grade 3 or 4 developed in 20 patients (61%), and acute gastrointestinal toxicity of grade 3 developed in 1 patient (3%). Vesicovaginal fistula occurred in 2 patients (6%). All patients achieved objective response (CR 70%, PR 30%) in 2 months after termination of treatment. One patient had a local progression in cervix, and 4 patients developed distant metastases. The 3-year estimated disease-free survival rates for stages I-IIA, IIB, III and IV were 67%, 91%, 88% and 50%, respectively. The 3-year estimated survival rates for stages I-IIA, IIB, III and IV were 89%, 91%, 88% and 50%, respectively. CONCLUSION: Concurrent chemoradiotherapy with paclitaxel and carboplatin is effective to achieve an excellent pelvic control.     

Radiation injury to intestine following hysterectomy and adjuvant radiotherapy for cervical cancer

OBJECTIVE: To evaluate the risk factors for nonrectal radiation-induced intestinal injury (NRRIII) following adjuvant radiotherapy (RT) for cervical cancer using a retrospective review of medical records. METHODS: From September 1992 to December 1998, 164 patients with uterine cervical cancer that had completed their allocated adjuvant radiotherapy at the Chinese Medical University Hospital were enrolled for NRRIII analysis. The patients were classified into two groups according to the extent of surgery. Group A consisted of 110 patients (International Federation of Gynecology and Obstetrics [FIGO] stage: IB, n = 87; IIA, n = 21; IIB, n = 2) undergoing radical hysterectomy and bilateral pelvic lymph node dissection, while Group B was composed of 54 analogs receiving adjuvant radiotherapy following incident extrafascial hysterectomy. Treatment consisted of external beam radiotherapy (EBRT) and high-dose-rate intravaginal brachytherapy (HDRIVB). Initially, the whole pelvis was treated with 10 MV X-rays. After irradiation (44 Gy in 22 fractions over 4-5 weeks), the field was limited to the true pelvis and a further 10-20 Gy delivered in 5-10 fractions. For 21 patients in group A without pelvic lymph node metastasis or lymphovascular invasion, the radiation field was confined to the lower pelvis, with a prescribed dose of 50-58 Gy delivered over 5-6 weeks. HDRIVB was performed using an Ir-192 remote after-loading technique at 1-week intervals. A total of 159 patients (97%) received two insertions, while 5 had only one. The standard prescribed HDRIVB dose was 7.5 Gy to the vaginal surface. Logistic regression analysis was performed for assessment of the factors associated with NRRIII. RESULTS: After 38-119 months of follow-up (median, 60), 22 patients (13.4%) developed Radiation Therapy Oncology Group (RTOG) grade 2 or greater NRRIII at a median latency of 18 months (range, 5-48). Four patients were diagnosed as grade 3 complications requiring surgery and three had expired. The independent factors for NRRIII were radical hysterectomy (P = 0.04, relative risk 2.45), lower-pelvic dose >54 Gy (P = 0.0001, relative risk 10.27), and age over 60 years (P = 0.001, relative risk 5.45). The incidence of NRRIII for patients receiving whole and lower-pelvic irradiation was 14.5% and 10.6%, respectively (P = 0.45). Although there was no statistical significance comparing the two external beam irradiation strategies in terms of NRRIII, all four patients with grade 3 NRRIII underwent whole pelvic irradiation. CONCLUSION: This study identifies three predictive factors for the development of NRRIII following adjuvant radiotherapy for cervical cancer. Limiting the EBRT dose to less than 54 Gy, meticulous patient selection in the elderly, careful planning of the irradiated field, and the constraint of vaginal brachytherapy are four approaches to optimization of postoperative adjuvant radiotherapy.     

Prostaglandin-induced cervical dilatation prior to intracavitary radiotherapy for carcinoma of the cervix: a pilot study

The efficacy of 1 mg 16,16-dimethyl-trans-Δ2 prostaglandin E1 (Gemeprost) pessaries in achieving cervical dilatation prior to intracavitary brachytherapy was investigated in 16 post-menopausal women with cervical carcinoma. All had received external beam pelvic radiotherapy in the preceding 6 weeks. Four patients were nulliparous and 12 multiparous (mean parity 1.9). FIGO stages were IB (2), IIA (4), IIB (5), IIIA (1), IIIB (3), IVB (1). The cervical os was assessed before pessary insertion and again at the time of intracavitary insertion. The os was closed in 100% (16/16) of patients before and open in 75% (12/16) of patients after pessary insertion. The maximum size of Hegar dilator passed without mechanical dila-tation was recorded. Mean cervical dilatation was 4.25 H (5.5 H in those with a clinical response). The 12 responding patients had rapid and uncomplicated procedures with no need for additional mechanical dilatation. Both patients in whom attempted mechanical dilatation failed had had previous conization of the cervix. The following mild side-effects were reported: abdominal cramps (43.8%), headache (12.5%) and fever (6.3%). These data support the use of Gemeprost pessaries to achieve cervical dilatation in post-menopausal women undergoing intracavitary brachy-therapy following external beam radiotherapy.     

Invasive squamous cell carcinoma of the cervix in women less than 35 years old: recurrent versus nonrecurrent disease

Invasive cervical squamous cell carcinoma was diagnosed in 45 patients less than 35 years old from 1980 to 1985. Thirty-two cases were Stage IB; 10, Stage IIB; and three, Stage IIIB. Twenty-two patients developed persistent or recurrent disease. Only one of these is now alive with no evidence of tumor. The mean interval from diagnosis to recurrence was 8.7 months (median of 7.0) and from diagnosis to death was 14.7 months (median of 12.0). Eleven of 32 patients with Stage IB disease developed a recurrence; the intervals to recurrence in Stage IB disease were similar to those for more advanced stages. Factors predicting recurrence included advanced stage of the disease and tumor bulk (maximum size, depth of invasion, and number of involved quadrants) as well as an exophytic or ulcerative tumor and a symptomatic presentation. These factors may identify the patient at high risk for recurrence who would benefit from adjuvant therapy.     

The American brachytherapy society survey of brachytherapy practice for carcinoma of the cervix in the United States

PURPOSE: The purpose of this study was to survey the brachytherapy practice for cervical cancer in the United States. METHODS: The Clinical Research Committee of the American Brachytherapy Society (ABS) performed a retrospective survey of individual physicians of the ABS and American Society of Therapeutic Radiologists and Oncologists regarding the details of the brachytherapy techniques they personally used in the treatment of cervical cancer patients for the year 1995. The replies (some of which may have been an estimate only) were tabulated. The scope of this survey did not allow us to verify the data by chart audits. RESULTS: A total of about 3500 questionnaires were mailed out; 521 responses were received. Of these responders, 206 (40%) did not perform any brachytherapy for carcinoma of the cervix in 1995. Of the other 315 responders reporting a total of 4892 patients treated in 1995, 88% used low dose rate (LDR) while 24% used high dose rate (HDR). There was a wide variation in the doses used. For LDR treatments, the median total external beam radiation therapy (EBRT) dose was 45 and 50 Gy and the LDR dose was 42 and 45 Gy for early and advanced cancers, respectively. For HDR treatments, the median EBRT dose was 48 and 50 Gy and the median HDR dose was 29 and 30 Gy for early and advanced cancers, respectively. The median dose per fraction was 6 Gy for a median of five fractions. Interstitial brachytherapy was used as a component of the treatment in 6% of the patients by 21% of responders. Very few responders treated with pulsed or medium dose rates. CONCLUSION: This retrospective survey showed the current brachytherapy practice pattern in the treatment of cervical cancer in the United States and can serve as a basis for future prospective national brachytherapy data registry. There was wide variation in the practice pattern, emphasizing the urgent need for consensus on these issues.     

252Cf中子腔内后装加盆腔外照射治疗子宫颈癌临床分析

目的观察^252Cf腔内后装加盆腔外照射治疗宫颈癌的疗效以及晚期并发症的发生情况,并对治疗方案进行总结。方法选择77例未接受过任何治疗的临床分期为Ⅱa～Ⅳa期的宫颈癌患者作为研究对象,其中Ⅱa期13例,Ⅱb期32例,Ⅲa期18例,Ⅲb期10例,Ⅳa期4例。治疗方案：^252Cf中子腔内后装治疗,宫旁A点剂量为8～11Gy／次,1次／周,共进行4～5次,使宫旁A点累积剂量达36～45Gy;该治疗过程中,间歇穿插前后对穿野全盆腔外照射200cGy／次,4次／周;外照射20—36Gy后,盆腔野中央屏蔽挡铅4cm,继续四野外照射200cGy／次,4次／周,使盆腔外照射总剂量达到45～50Gy左右。总疗程约需5—6周。结果77例患者随访3年,3年局部控制率为94％(72／77);3年总生存率为82％(63／77),其中临床分期Ⅱa期为85％(11／13),Ⅱb期为94％(30／32),Ⅲa期为78％(14／18),Ⅲb期为70％(7／10),Ⅳa期为1／4。放射性膀胱炎发生率为3％,放射性直肠炎发生率为5％。结论^252Cf中子腔内后装加盆腔外照射治疗宫颈癌,患者能较好耐受,且其Ⅱ、Ⅲ期患者的3年生存率较高而并发症发生率较低,具有较好的应用前景。     

Discrepancies between clinical staging and pathological findings of operable cervical carcinoma with stage IB–IIB: A retrospective analysis of 818 patients

Introduction and objectives:  Cervical cancer is the only gynaecological cancer that is staged clinically. The clinical stage of cervical cancer relies largely on the pelvic examination. The aim of this study is to analyse the discrepancy between clinical stage and pathological results, and to explore the accuracy of pelvic examination.
Methods:  We collected retrospective data from 818 patients with cervical carcinoma staged IB–IIB, who were treated with primary surgery from January 1999 to June 2007. Clinical stages of those patients were determined by pelvic examination without anaesthesia. After surgery, all the patients were assigned to pT category according to the pathological findings. Comparisons were made between these two stages.
Results:  The total concordance between clinical stage and pT category for stage IB–IIB was 53.1%, with an overestimation of 37.3% and an underestimation of 9.7%. The concordance in stage IB1, stage IB2, stage IIA and stage IIB were 85.4%, 77.4%, 35.3% and 20.5%, respectively. The most significant discrepancy was caused by the failure to detect the parametrial invasion accurately in stage IIB. The accuracy of pelvic examination to determine vaginal and parametrial disease was 70.2% and 74.0%, respectively.
Conclusions:  There are significant discrepancies between clinical stage and pathological results. Pelvic examination has its limitations in staging determination. Thus for operable cervical cancer, clinical stage alone is not reliable for selecting postoperative therapies and surgical staging system may be considered.     

Neoadjuvant chemotherapy with cisplatin, ifosfamide and 5-fluorouracil in the treatment of locally advanced cervical cancer

Abstract. Etcheverry MG, Marantz A, Saine M, Litovska S, Lewi D, Cecchin G, Nuñez de Pierro A. Neoadjuvant Chemotherapy in the treatment of locally advanced cervical cancer.
The objective of this study was to evaluate clinical and histological response, resectability, and survival in patients with cervical epidermoid carcinoma stage IB2 to IIIB with the use of neoadjuvant chemotherapy followed by radical surgery and/or radiation therapy. Between September 1989 and February 1996, 53 patients were admitted to this study. They were given three cycles of cisplatin 30 mg/m²/day, 5-fluorouracil 500 mg/m²/day, ifosfamide 2000 mg/m²/day i.v., and mesna 400 mg/m²/day i.v. at hour 0 and 400 mg/m² at hours 4 and 8 during three days every 21–28 days. We evaluated 47 patients. Global clinical response obtained was 85%{95% (CI), 75–97%, CR in 14 patients (30%) and PR in 26 patients (55%)}. Twenty-three patients underwent surgery. Six patients (13%) had a complete histological response. Median follow-up was 42 months (5–96). In resected patients, with a median follow-up of 57 months (5–96), the estimated five-year disease-free survival was 78%. Global survival estimated to 60 months was 83% for stage IB2, 70% for IIB, and 20% for IIIB. This mode of therapy offers a new option to improve survival in locally advanced cervical cancer. Randomized trials are required in order to establish a definitive role for this therapeutic strategy.