J. Taylor Wharton

Quality of Life and Sexual Functioning in Cervical Cancer Survivors

PURPOSE To compare quality of life and sexual functioning in cervical cancer survivors treated with either radical hysterectomy and lymph node dissection or radiotherapy. METHODS Women were interviewed at least 5 years after initial treatment for cervical cancer. Eligible women had squamous cell tumors smaller than 6 cm at diagnosis, were currently disease-free, and had either undergone surgery or radiotherapy, but not both. The two treatment groups were then compared using univariate analysis and multivariate linear regression with a control group of age- and race-matched women with no history of cancer. RESULTS One hundred fourteen patients (37 surgery, 37 radiotherapy, 40 controls) were included for analysis. When compared with surgery patients and controls using univariate analysis, radiation patients had significantly poorer scores on standardized questionnaires measuring health-related quality of life (physical and mental health), psychosocial distress and sexual functioning. The disparity in sexual function remained significant in a multivariate analysis. Univariate and multivariate analyses did not show significant differences between radical hysterectomy patients and controls on any of the outcome measures. CONCLUSION Cervical cancer survivors treated with radiotherapy had worse sexual functioning than did those treated with radical hysterectomy and lymph node dissection. In contrast, these data suggest that cervical cancer survivors treated with surgery alone can expect overall quality of life and sexual function not unlike that of peers without a history of cancer.

THE INFLUENCE OF TUMOR SIZE AND MORPHOLOGY ON THE OUTCOME OF PATIENTS WITH FIGO STAGE IB SQUAMOUS CELL CARCINOMA OF THE UTERINE CERVIX

PURPOSE To define the influence of tumor size and morphology on rates of central tumor control (CTC), pelvic tumor control (PTC), and disease-specific survival (DSS) in patients treated with radiotherapy for squamous cell carcinoma of the intact uterine cervix. METHODS AND MATERIALS Records of 1526 patients treated with radiotherapy for FIGO Stage IB squamous cell carcinoma of the intact uterine cervix between 1960 and 1989 were retrospectively reviewed. The maximum tumor or cervical diameter was determined from clinical descriptions for 1494 patients. Tumors were divided into nine size categories. Tumors > or = 4 cm were further classified according to the dominant morphology (i.e., exophytic or endocervical). Median follow-up was 12.2 years. Five-year CTC, PTC, and DSS rates were calculated actuarially. RESULTS CTC, PTC, and DSS rates correlated strongly with tumor diameter (p < 0.0001). Overall, CTC, PTC, and DSS rates for patients with tumors < 5 cm were 99%, 97%, and 88%, respectively. For patients with tumors 5-7.9 cm these rates were 93%, 84%, and 69%, respectively. There were no significant differences in the rates of PTC, CTC, or DSS between subgroups of patients with lesions 5-7.9 cm in diameter. The rates of CTC (97%) and DSS (76%) for patients with 5-7.9 cm exophytic tumors were significantly better than those for patients with endocervical tumors of the same size (91% and 66%, respectively); there was no difference in the PTC rate. CONCLUSION Although the CTC rates were excellent for all patients with tumors < 8 cm in diameter, these rates for tumors < 5 cm (99%) and for exophytic tumors 5-7.9 cm (97%) make it difficult to justify the use of adjuvant hysterectomy. Although patients with tumors of 5-7.9 cm had consistently poorer PTC and DSS rates than did patients with smaller tumors, the control rates achieved with aggressive radiotherapy were still excellent. The strong correlation between tumor size and outcome suggests that tumor diameter should be assessed when tumors are clinically evaluated and staged and when treatment results are reported for patients with FIGO Stage IB carcinoma of the uterine cervix.

Rankings and symptom assessments of side effects from chemotherapy: Insights from experienced patients with ovarian cancer

Goals of workAlthough many patients with ovarian cancer achieve favorable responses to primary chemotherapy, the majority of women will experience recurrence of their cancer. Selection of second- or third-line chemotherapy ultimately depends on patient preferences for different side effects. To better understand this process, we evaluated preferences and symptom distress in patients with ovarian cancer.Patients and methodsA total of 70 women with ovarian cancer who had previously received at least three cycles of platinum-based chemotherapy and currently undergoing chemotherapy for newly diagnosed or recurrent disease were interviewed in an outpatient chemotherapy clinic. The patients were asked to rank order 27 health states using a modified visual analog scale and to complete the Memorial Symptom Assessment Scale (MSAS).Main resultsMost favorable health states included perfect health, clinical remission and complete control of chemotherapy-induced nausea and vomiting (CINV). Least favorable health states included more severe CINV health states and death. Patients on first-line chemotherapy had less symptom distress, and rated sexual dysfunction, fatigue and memory loss more favorably than patients on second- or third-line chemotherapy (P<0.05). Married patients generally had less symptom distress compared to patients who were not married, but married patients indicated more distress with sexual dysfunction (P=0.04). Married patients rated alopecia less favorably than unmarried patients (P=0.03), but married patients viewed certain CINV health states more favorably (P=0.02–0.04).ConclusionsCINV remains one of the most dreaded side effects of chemotherapy. Separate preference profiles exist for patients with newly diagnosed and recurrent disease, as well as for married versus unmarried patients. While MSAS scores and VAS rankings showed consistency across some health states, this was not true for CINV, suggesting that current symptom status may only influence patient preferences for selected side effects.

Adenocarcinoma of the uterine cervix prognosis and patterns of failure in 367 cases

Between 1965 and 1985, 367 patients received initial treatment for adenocarcinoma of the uterine cervix at the M. D. Anderson Cancer Center (MDACC). Of the 334 patients treated with curative intent, 223 had International Federation of Gynecology and Obstetrics (FIGO) Stage I, 60 had Stage II, and 51 had Stage III/IV disease. The 5‐year and 10‐year relapse‐free survival (RFS) rates for all patients treated for Stage I disease were 73% and 70%, respectively. RFS was strongly correlated with initial bulk of disease (P = 0.002), although locoregional control (LRC) was good in all groups: 91 patients with a normal‐sized cervix (tumor < 3 cm) had a 5‐year RFS rate of 88% and an actuarial LRC rate of 94%; 102 patients with lesions 3 to 5.9 cm in diameter had an RFS rate of 64% and an LRC rate of 82%; and 22 patients with bulky lesions greater than 6 cm in diameter had a comparable LRC rate of 81%, but an RFS rate of only 45%. Decreased RFS also was strongly correlated with positive lymphangiogram (LAG) results (P = 0.02) and poorly differentiated lesions (P = 0.0014). When initial primary tumor size was taken into account, there was no significant difference in RFS or LRC between patients treated with radiation (RT) alone or RT plus extrafascial hysterectomy (R + S). The 5‐year and 10‐year RFS rates of 60 patients who received curative therapy for Stage II disease were 32% and 25%, respectively, with an LRC rate of 62% at 5 years. Patients with bulky Stage II disease did particularly poorly, with a 5‐year RFS rate of 15%. Decreased RFS was correlated with positive LAG results and poorly differentiated tumors. Most Stage II patients whose disease relapsed died with distant metastases (73%). Forty‐eight patients with Stage III/IV disease treated with curative intent had a 5‐year survival rate of 31% and a 5‐year pelvic disease control rate of 52%. In summary, patients with small volume Stage IB lesions have excellent LRC and survival with RT alone. RT achieves good LRC of bulkier Stage I lesions, but survival decreases with increasing primary tumor size. R + S holds no apparent advantage over RT alone. Patients with more advanced disease have a high rate of relapse with frequent distant metastasis. In particular, the survival of patients with FIGO Stage II disease is much lower than what we have observed after treatment of comparable stage squamous carcinoma. However, the late recurrences and prolonged natural history experienced by a few patients suggest a broad spectrum of biologic aggressiveness among cervical adenocarcinomas.

Outcome and reproductive function after Conservative surgery for borderline ovarian tumors

Objective: To study reproductive function and disease outcome in women with borderline ovarian tumors who were treated with conservative surgery. Methods: Patients with borderline ovarian tumors were identified from institutional databases. Patients were eligible if they had pathologically confirmed borderline ovarian tumors, no prior sterilization, no history of radiation therapy, retained their uterus and ovarian tissue, and were younger than age 45. Information was acquired by retrospective medical record review and patient interview. Results: Forty-three patients met the eligibility criteria. The median age was 25 years, with a range of 15‐39 years. Twenty-six patients had serous tumors, and 17 had mucinous tumors. Fifteen had stage I disease, three had stage III, and 25 were unstaged. Follow-up was available for all patients (median, 5.7 years). Twenty-nine remained diseasefree, and 14 developed a new primary lesion/recurrence, with a median time to recurrence of 39.3 months. Recurrence was more frequent in patients treated with ovarian cystectomy than in those treated with oophorectomy alone (58% compared with 23%) (P < .04). After treatment, 29 of 36 patients (81%) retained normal menstrual cycles, and 12 of 24 patients attempting pregnancy conceived 25 pregnancies. Most patients were highly satisfied with conservative surgery. Conclusion: Conservative surgery remains a therapeutic option in selected patients with borderline ovarian tumors. Although the rate of new lesion/recurrence is relatively high, especially in those treated with ovarian cystectomy, mortality from cancer remains low. Many patients who desire pregnancy are able to conceive and deliver healthy offspring after conservative surgery. (Obstet Gynecol 2000;95:541‐7.

Outcome and Reproductive Function After Chemotherapy for Ovarian Dysgerminoma

PURPOSE To review the outcome for all patients with ovarian dysgerminoma treated at the M.D. Anderson Cancer Center who received bleomycin, etoposide, and cisplatin (BEP) and to assess the menstrual and reproductive function of those who received conservative treatment. PATIENTS AND METHODS Clinical information was abstracted from the medical record. Patients completed a detailed questionnaire about menstrual and reproductive function; those who did not return the questionnaire were interviewed by telephone. RESULTS Twenty-six patients were identified as having been treated with BEP chemotherapy for pure ovarian dysgerminoma from January 1984 to January 1998. Their median age was 19.5 years (range, 7 to 32 years). Sixteen patients underwent fertility-sparing surgery in the form of unilateral salpingo-oophorectomy. At a median follow-up time of 89 months, 25 (96%) of the 26 patients remained continuously disease-free. One patient apparently developed a second primary dysgerminoma in her remaining ovary after BEP and was clinically disease-free after further treatment. Of the 16 patients who underwent fertility-sparing surgery, one was lost to follow-up when she was pregnant, and one was still premenarchal. Of the remaining 14 patients, 10 (71%) maintained their normal menstrual function during and after chemotherapy, and 13 (93%) had returned to their prechemotherapy menstrual pattern at the time of the questionnaire. Five pregnancies have occurred thus far, and two patients have had difficulty conceiving. CONCLUSION Most patients with metastatic dysgerminoma can expect cure with maintenance of normal reproductive function when treated with conservative surgery and BEP chemotherapy.

Definitive radiotherapy for carcinoma of the vagina: Outcome and prognostic factors

PURPOSE Primary carcinoma of the vagina is an uncommon tumor. Because of the long-standing interest in this disease at our institution a substantial number of patients with this disease has been accumulated, and this retrospective review was performed to define disease outcome, to delineate significant prognostic factors, and to provide treatment guidelines. METHODS AND MATERIALS This was a retrospective review of 301 patients with vaginal carcinoma (271 with squamous cell and 30 with adenocarcinoma) who received definitive radiotherapy between 1953 and 1991. Prognostic factors for outcome (local control, pelvic control, metastatic relapse, survival, and complications) were evaluated using univariate and multivariate techniques. RESULTS Patients disease was staged using the International Federation of Gynecology and Obstetrics (FIGO) system, and stages were distributed as follows: 0, 37 (12%); I, 65 (22%); II, 122 (40%); III, 60 (20%); and, IVA, 17 (6%). Treatment varied according to stage, with brachytherapy predominating for early disease but external beam playing a prominent role for more advanced disease. Patients with in situ disease received brachytherapy alone or transvaginal orthovoltage irradiation. For Stage I, brachytherapy alone was used in 25, external beam and brachytherapy in 38, and transvaginal alone in 2. For Stage II, brachytherapy alone was used in 20, external and brachytherapy in 66, and external irradiation alone in 36. For Stage III, external and brachytherapy was used in 15, and external alone in 45. Two patients with Stage IVA received brachytherapy alone, 10 received a combination of external and brachytherapy, and 6 received external irradiation alone. Total doses ranged from 10 to 154 Gy (mean 74.7 Gy, median 70.0 Gy), but only 18 (6%) received less than 55 Gy. At a median follow-up of 13 years, the 5-, 10-, 15-, 20-, and 25-year survival rates were 60%, 49%, 38%, 29%, and 23%, respectively. Beyond 5 years the survival rates relative to those for age-matched females in the general population were between 50 and 65%. Actuarial local recurrence rates were 23%, 26%, and 26% at 5, 10, and 15 years. Actuarial pelvic relapse rates were 26%, 30%, and 31% at 5, 10, and 15 years, and metastatic rates at those times were 15%, 18%, and 18%. Adenocarcinoma (nonclear cell) was a significantly worse disease than squamous cell carcinoma. The major determinants of local control for squamous carcinoma were tumor bulk (specified by size in centimeters, or by FIGO stage), tumor site (upper lesions faring better than others), and tumor circumferential location (lesions involving the posterior wall faring worse). Tumor bulk was an important determinant of metastatic relapse, but failure to achieve local control was also an independently significant determinant of metastases. Salvage after first relapse was uncommon and the survival rate at 5 years after relapse was only 12%. Serious complications occurred in 39 patients with an actuarial incidence of 19% at 20 years. CONCLUSION Vaginal carcinoma poses a formidable therapeutic challenge. The disease is heterogeneous with respect to its prognostic factors. Nonclear cell adenocarcinoma has an extremely poor prognosis and should be distinguished from squamous carcinoma. Both external beam and brachytherapy play crucial roles in management and most patients with disease beyond in situ should receive a significant component of external irradiation prior to brachytherapy.

Treatment of poor-prognosis sex cord-stromal tumors of the ovary with the combination of bleomycin, etoposide, and cisplatin

Objective To investigate the clinical activity of the combination of bleomycin, etoposide, and cisplatin for metastatic ovarian sex cord-stromal, cord-stromal tumors of all types and poorly differentiated Sertoli-Leydig cell tumors confined to the ovary. Methods The regimen was administered as follows: bleomycin 10–15 mg/day by continuous intravenous (IV) infusion on days 1–3; etoposide 100 mg/m2 IV per day on days 1–3; cisplatin 100 mg/m2 IV on day. 1. End points for analysis included response, progression-free survival, and survival. Results Nine patients were entered in this trial. The median age was 37 years (range 12–69). Histologic types included adult granulosa cell tumor in five patients, juvenile granulosa cell tumor in one, poorly differentiated Sertoli-Leydig cell tumor in two, and mixed tumor in one. Stage distribution was as follows: stage Ia, two: stage IIc, one; stage IIc, one; recurrent, five. Of the six patients with measurable disease, two (33%) had a complete response (one surgical and one clinical), and three (50%) had a partial response, for an overall response rate of 83%l; one patient had no response. Toxicity was acceptable; two patients had mild bleomycin pulmonary toxicity. Of the three patients with nonmeasurable disease, one relapsed, one developed progressive disease, and one remains in remission. Of the seven patients with metastatic disease, only one (14%) had a durable remission. Median progression-free survival was 14 months. Median survival time was 28 months. At the time of analysis, two patients alive disease-free, three were alive with disease, and four were dead of disease. Conclusion Although the overall response rate to the combination of bleomycin, etoposide, and cisplatin was high, the regimen apparently lacks durable activity in this groups of tumors. More active drugs and modalities should continue to be investigated.

Uterine papillary serous carcinoma (UPSC) treated with cisplatin, doxorubicin, and cyclophosphamide (PAC)

Uterine papillary serous carcinoma (UPSC) is an aggressive malignancy that accounts for a disproportionate number of intraabdominal failures among endometrial carcinoma patients. The histologic appearance and tendency toward intraabdominal spread resemble those of papillary serous adenocarcinoma of the ovary. Because approximately 70% of untreated ovarian carcinoma patients respond to platinum-based chemotherapy, it has been suggested that UPSC patients might respond to similar treatment regimens. Twenty patients with UPSC were treated with cisplatin, doxorubicin (Adriamycin), cyclophosphamide (PAC) chemotherapy between January 1982 and December 1989. They included 9 patients with advanced primary disease, 5 with recurrence, and 6 who received PAC as adjuvant therapy. Patients received a mean of five cycles of PAC. Only 2 of 11 patients with measurable disease greater than 2 cm achieved complete clinical responses of 12 and 31 months duration; there were no partial responses. Actuarial 5-year survival for all patients was 23%. The mean progression-free interval was 9 months. Patients with clinical stages I or II disease had a higher survival rate than those with stage III or IV disease (P = 0.003). Survival did not correlate with depth of myometrial invasion (P = 0.81) or size of residual tumor following initial surgery (P = 0.16). Estrogen or progesterone receptors were detected in 10 of 11 tumors tested. Seven of 9 patients tested had elevated serum levels of CA-125 (greater than 35 U/ml). Correlation between CA-125 value and clinical course was demonstrated in 3 of 5 patients who had serial measurements. Of all patients, 3 are currently alive; 1 has documented disease. Moderate to severe toxicity was seen in 14 patients (70%). There was one possible treatment-related death from cardiomyopathy. UPSC, despite its histologic and clinical similarities to ovarian carcinoma, was relatively resistant to PAC chemotherapy in this mixed group of patients.

Extramammary Paget's disease of the perineal skin : role of radiotherapy

We have reviewed our treatment results in 65 patients with extramammary Pagets disease arising in the vulva, perianal area, or scrotum. In 30 patients with primary disease, positive surgical margins were found in 53%, and there was an actuarial local recurrence rate of 40% within 5 years. The median follow-up period for primary extramammary Pagets disease patients treated with surgery alone was 198 months, and none died of this disease. Three patients treated with definitive radiotherapy were without recurrence at 12, 21, and 60 months after 56 Gy of supervoltage x-rays. In 22 patients with extramammary Pagets disease and associated adnexal or rectal adenocarcinoma, nine treated with surgery alone had a 75% local control rate. Three patients treated with surgery and adjuvant radiotherapy all had local control; of two patients treated with radiotherapy alone, one had persistent adenocarcinoma. The median survival for all patients with extramammary Pagets disease and adenocarcinoma was 22 months. We conclude that patients with extramammary Pagets disease have excellent survival but that local recurrence and morbidity from surgery, especially in the elderly, can be high. Radiotherapy greater than 50 Gy as primary treatment for extramammary Pagets disease in those medically unfit for surgery, or as an alternative to further surgery for recurrence after surgery and for anyone wishing to avoid mutilating surgery, is indicated. For those with adenocarcinoma and extramammary Pagets disease, the use of adjuvant postoperative radiotherapy in doses greater than 55 Gy is indicated because of the high risk of local recurrence after surgery alone.