-
[show abstract]
[hide abstract]
ABSTRACT: To determine the efficacy and toxicity of radiation therapy and concurrent weekly cisplatin chemotherapy in achieving a complete clinical and pathologic response when used for the primary treatment of locally-advanced vulvar carcinoma.
Patients with locally-advanced (T3 or T4 tumors not amenable to surgical resection via radical vulvectomy), previously untreated squamous cell carcinoma of the vulva were treated with radiation (1.8 Gy daily × 32 fractions=57.6 Gy) plus weekly cisplatin (40 mg/m(2)) followed by surgical resection of residual tumor (or biopsy to confirm complete clinical response). Management of the groin lymph nodes was standardized and was not a statistical endpoint. Primary endpoints were complete clinical and pathologic response rates of the primary vulvar tumor.
A planned interim analysis indicated sufficient activity to reopen the study to a second stage of accrual. Among 58 evaluable patients, there were 40 (69%) who completed study treatment. Reasons for prematurely discontinuing treatment included: patient refusal (N=4), toxicity (N=9), death (N=2), other (N=3). There were 37 patients with a complete clinical response (37/58; 64%). Among these women there were 34 who underwent surgical biopsy and 29 (78%) who also had a complete pathological response. Common adverse effects included leukopenia, pain, radiation dermatitis, pain, or metabolic changes.
This combination of radiation therapy plus weekly cisplatin successfully yielded high complete clinical and pathologic response rates with acceptable toxicity.
Gynecologic Oncology 11/2011; 124(3):529-33. · 3.89 Impact Factor
-
Gynecologic Oncology 07/2011; · 3.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the outcome of stage IVA cervical cancer treated with radiation and concurrent cisplatin-based chemotherapy.
We conducted a retrospective study of stage IVA cervical cancer patients from four trials (Gynecologic Oncology Group protocols 56, 85, 120, and 165) treated with radiotherapy with or without concurrent cisplatin-based chemotherapy. Patient records were reviewed for demographic and tumor features, treatment, and progression-free survival (PFS) and overall survival (OS). Stage IVA patients were compared to stage IIIB patients from these same studies.
Among the 51 stage IVA patients studied, 92% were stage IVA on the basis of bladder involvement. The median PFS was 10.1 months (95% CI=6.3-14.5 months) and median OS was 21.2 months (95% CI=13.3-30.5 months). The 3 year survival was 32%. On univariate analysis, only advanced age was associated with OS (p=0.0115) but age had only marginal effect on PFS (p=0.083). Pathologic proven pelvic nodal metastasis was of marginal significance for both PFS and OS, p=0.059 and 0.064, respectively. Despite similar patient characteristics, the use of cisplatin-based chemotherapy had no impact on PFS or OS but was underpowered to address this question. When compared to stage IIIB patients, stage IVA patients had a poorer performance status (p=0.0231), larger tumor size (p=0.0302), and more frequent bilateral parametrial involvement (0.0063).
Patients with stage IVA disease had poor median survival of only 21 months with only 32% 3 year survival. Stage IVA patients have larger tumor size, more bilateral parametrial involvement, and poorer survival when compared to stage IIIB patients.
Gynecologic Oncology 03/2011; 121(3):542-5. · 3.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The objective of the study was to study posttherapy chemoradiation hysterectomy histology with long-term survival in bulky stage 1(B) cervical cancer patients.
Gynecologic Oncology Group protocols 71 and 123 enrolled 464 patients randomly allocated to pelvic radiation (75 Gy, n = 291) plus hysterectomy (RTH) or to pelvic radiation (75 Gy) and cisplatin (40 mg/m(2), n = 176) plus hysterectomy (RTCH). Risk of progression and death were evaluated by posttherapy hysterectomy response (good: <10% viable; poor: ≥10% viable).
Median survivor follow-up was 112 months. Relative risks of disease progression and death were 0.656 (95% confidence interval, 0.472-0.912) and 0.638 (95% confidence interval, 0.449-0.908), favoring RTCH. Good response patients (345; 74%) had similar 10 year overall survival (OS) and progression-free survival (PFS) after RTH or RTCH (P > .47). Poor response patients after RTCH had superior OS (P = .046) and PFS (P = .084). Extrapelvic recurrences occurred more often in poor response patients.
Posttherapy viable residual disease less than 10% was associated with reduced risk of progression and cancer-related death.
American journal of obstetrics and gynecology 10/2010; 203(4):351.e1-8. · 3.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To estimate the significance of hydronephrosis and impact of ureteral obstruction relief on outcome in patients with stage IIIB cervical cancer treated with radiation and concurrent chemotherapy.
We retrospectively studied stage IIIB cervical cancer patients treated on GOG trials 56, 85, 120 and 165 evaluating radiation and concurrent chemotherapy. Eligible patient records were reviewed to assess the presence of hydronephrosis and treatment of ureteral obstruction. Patients were classified into three groups; no hydronephrosis, hydronephrosis relieved from ureteral obstruction via stent or percutaneous nephrostomy and hydronephrosis without treatment of ureteral obstruction.
539 stage IIIB patients were studied. Hydronephrosis was present in 238 (44.2%). Patient age, race, and tumor characteristics (size, histology and grade) were not significantly different between patients with or without hydronephrosis. Patients with hydronephrosis received similar doses of radiation and cisplatin-based chemotherapy. Both overall and progression-free survival were worse with hydronephrosis (log-rank test p value=0.0189 and 0.0186, respectively). Univariable analysis identified five prognostic factors; pelvic nodal metastasis (p=0.0001), tumor diameter (p=0.0007), cisplatin-based concurrent chemoradiation (p=0.0031), hydronephrosis (p=0.0189), and performance status (p=0.0359). Hydronephrosis was associated with worse performance status (p<0.001). On multivariable analysis hydronephrosis was not a significant prognostic factor. Ureteral obstruction relief occurred for 88% of patients and was associated with improved survival.
In patients with stage IIIB cervical cancer restricted to the pelvis, hydronephrosis at presentation is a significant but not independent prognostic factor associated with poor performance status and poorer survival. Relief of ureteral obstruction is correlated with improved outcome.
Gynecologic Oncology 02/2010; 117(2):270-5. · 3.89 Impact Factor
-
Gynecologic Oncology 05/2009; 113(1):1-3. · 3.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine if low node count from superficial groin dissection correlated with first recurrence in the groin for patients with early vulvar cancer.
The Gynecologic Oncology Group (GOG) conducted a trial for patients with early stage squamous vulvar cancer, lesions <2 cm in size and <5 mm in depth. All fatty tissue below the inguinal ligament, medial to the sartorious and lateral to the adductor longus was removed. Incision of the fascia and skeletonizing the femoral vessels were not required. For this secondary analysis, we reviewed the records of all patients to assess node counts.
Of the 113 patients eligible for the study, 104 patients (with 117 dissected groins) did not have a first recurrence in the groin. The median number of negative nodes was 9 (range: 1-26). Nine patients (with 9 dissected groins) suffered a first recurrence in the groin. The median number of negative nodes removed per groin was 7 (range: 4-22). There were no significant differences between patients with first recurrence in the groin and those without (p value=0.7475). There was a broad overlap of the confidence intervals.
We were unable to show that groin failure after superficial lymphadenectomy was a result of low lymph node count. The small number of recurrences made firm conclusions impossible. Variations in anatomy and other factors may make node counting an unreliable measure of surgical quality.
Gynecologic Oncology 02/2009; 113(1):52-6. · 3.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine whether maintaining HGB levels > or = 12.0 g/dL with recombinant human erythropoietin (R-HUEPO) compared to "standard" treatment (transfusion for HGB < or = 10.0 g/dL) improves progression-free survival (PFS), overall survival (OS) and local control (LC) in women receiving concurrent weekly cisplatin and radiation (CT/RT) for carcinoma of the cervix. In addition, to determine whether platinum-DNA adducts were associated with clinical characteristics or outcome.
Patients with stage IIB-IVA cervical cancer and HGB < 14.0 g/dL were randomly assigned to CT/RT+/-R-HUEPO (40,000 units s.c. weekly). R-HUEPO was stopped if HGB > 14.0 g/dL. Endpoints were PFS, OS and LC. Platinum-DNA adducts were quantified using immunocytochemistry assay in buccal cells.
Between 08/01 and 09/03, 109 of 114 patients accrued were eligible. Fifty-two received CT/RT and 57 CT/RT+R-HUEPO. The study closed prematurely, with less than 25% of the planned accrual, due to potential concerns for thromboembolic event (TE) with R-HUEPO. Median follow-up was 37 months (range 9.8-50.4 months). PFS and OS at 3 years should be 65% and 75% for CT/RT and 58% and 61% for CT/RT+R-HUEPO, respectively. TE occurred in 4/52 receiving CT/RT and 11/57 with CT/RT+R-HUEPO, not all considered treatment related. No deaths occurred from TE. High-platinum adducts were associated with inferior PFS and LC.
TE is common in cervical cancer patients receiving CT/RT. Difference in TE rate between the two treatments was not statistically significant. The impact of maintaining HGB level > 12.0 g/dL on PFS, OS and LC remains undetermined.
Gynecologic Oncology 02/2008; 108(2):317-25. · 3.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The objective of the study was to confirm that concurrent cisplatin (CT) with radiation therapy (RT) is associated with improved long-term progression-free survival (PFS) and overall survival (OS), compared with RT alone in stage IB bulky carcinoma of the cervix, when both groups' therapy is followed by hysterectomy.
Three hundred seventy-four patients entered this trial. There were 369 evaluable patients; 186 were randomly allocated to receive RT alone and 183 to receive CT plus RT. Radiation dosage was 45 Gray (Gy) in 20 fractions followed by low dose-rate intracavitary application(s) of 30 Gy to point A. Chemotherapy consisted of intravenous cisplatin 40 mg/m2 every week for up to 6 weekly cycles. Total extrafascial hysterectomy followed the completion of RT by 6-8 weeks.
Preliminary results have been published, at which time there were 292 censored observations, and median duration of follow-up was only 36 months. Patient and tumor characteristics were well balanced between the regimens. The median patient age was 41.5 years; 81% had squamous tumors; 59% were white. Median follow-up is now 101 months. The relative risk for progression was 0.61 favoring CT plus RT (95% confidence interval [CI] 0.43 to 0.85, P < .004). At 72 months, 71% of patients receiving CT plus RT were predicted to be alive and disease free when adjusting for age and tumor size, compared with 60% of those receiving RT alone. The adjusted death hazard ratio was 0.63 (95% CI 0.43 to 0.91, P < .015) favoring CT plus RT. At 72 months, 78% of CT plus RT patients were predicted to be alive, compared with 64% of RT patients. An increased rate of early hematologic and gastrointestinal toxicity was seen with CT plus RT. There was no detectable difference in the frequency of late adverse events.
Concurrent weekly cisplatin with RT significantly improves long-term PFS and OS when compared with RT alone. Serious late effects were not increased. The inclusion of hysterectomy has been discontinued on the basis of another trial. Pending further trials, weekly cisplatin with radiation is the standard against which other regimens should be compared.
American journal of obstetrics and gynecology 11/2007; 197(5):503.e1-6. · 3.28 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We report the long-term survival and toxicity of a randomized phase III study comparing cisplatin alone with cisplatin, flurouracil, and hydroxyurea versus hydroxyurea concurrent with pelvic irradiation for patients with locally advanced cervical cancer with pathologically negative para-aortic nodes.
Comparisons of progression-free (PFS) and overall survival (OS) between treatment arms utilized Kaplan-Meier and log-rank statistics. Relative risk estimates adjusting for prognostic factors were determined using the Cox proportional hazards regression model. Pearson's 2 test was used to assess differences in adverse events.
The analysis included 526 patients. The median follow-up among surviving patients was 106 months. Consistent with the original report, improvement in PFS and OS was evident for both cisplatin-containing arms compared with hydroxyurea (P < .001). Analogous results were seen for stage IIB and for stage III disease (each P < .025). The relative risk of progression of disease or death was 0.57 (95% CI, 0.43 to 0.75) with cisplatin and 0.51 (95% CI, 0.38 to 0.67) with cisplatin-based combination chemotherapy compared with hydroxyurea. Among 518 patients who received radiation, acute (grade 3 or 4) gastrointestinal or urologic toxicities occurred in 66 with cisplatin (19.1%) and 29 with hydroxyurea (16.8%). Delayed radiation toxicity occurred in six patients who received cisplatin (1.7%) and two who received hydroxyurea (1.2%; P = .680).
Cisplatin-based chemotherapy during pelvic radiation therapy improves long-term PFS and OS among locally advanced cervical cancer patients collectively and for stage IIB and III disease, individually. There was no observed increase in late toxicity with cisplatin-based chemoradiotherapy.
Journal of Clinical Oncology 07/2007; 25(19):2804-10. · 18.37 Impact Factor
