Allan J. Jacobs

Carcinoma of the fallopian tube: management and sites of failure

Thirty patients with adenocarcinoma of the fallopian tube, treated between 1950 and 1981, were studied. Median age was 55 years, and mean parity was 1.3. Bleeding or discharge occurred as a presenting complaint in 47% of patients, abdominal distention or mass in 50%, and pain in 30%. Lesions were staged using a system analogous to the International Federation of Gynecology and Obstetrics (FIGO) classification for ovarian carcinoma. Nine patients had Stage I disease; 11, Stage II; 7, Stage III; and 3, Stage IV. Histologic differentiation was Grade 1 in 39% of the patients, Grade 2 in 18%, and Grade 3 in 43%. Primary surgical treatment consisted of total abdominal hysterectomy and bilateral salpingectomy in 70% of the patients; 23% had more extensive surgery, whereas 13% had less extensive surgery. Three patients with Stage I tumors were treated with surgery alone, and the remainder received postoperative radiation, chemotherapy, or both. Survival was unrelated to grade, but highly dependent upon stage. Survival at 5 years was 56% for Stage I, 27% for Stage II, 14% for Stage III, and 0% for Stage IV. Four of five patients treated after surgery with a combination of cisplatin, doxorubicin, and cyclophosphamide (PAC) survived at least 3 years. Patterns of initial treatment failure showed 56% with a component of pelvic failure, 50% with a component of upper abdominal failure, and 44% with extraperitoneal metastases as a component of failure. These results suggest the need for aggressive postoperative adjuvant therapy targeted at upper abdominal and distant sites for metastasis in all lesions beyond Stage I.

Serum levels of CA-125 in patients with endometriosis: a preliminary report

Seven out of 8 patients with endometriosis demonstrated levels of CA-125 antigen above 35 U/ml. None of 15 patients with other benign gynecologic diagnoses demonstrated elevated levels. This antigen has been proposed as a tumor marker for epithelial carcinoma and other gynecologic neoplasms. However, it cannot be used to differentiate clinically between cancer and endometriosis.

Short-term persistence of carcinoma of the uterine cervix after radiation. An indicator of long-term prognosis.

Between 1959 and 1980, 590 evaluable patients received a full course of radiation therapy as primary treatment of invasive epidermoid carcinoma of the cervix. At follow‐up visits conducted between 1 and 3 months after the completion of radiation, 72 patients had physical or biopsy findings indicative of persistent disease (PER), whereas an additional 36 had findings suggestive of tumor (SUS). The remaining 482 demonstrated a complete response (CR) by 1 month after the administration of treatment. The lower the stage, the more likely was a CR by 3 months (Stage I, 94.4%; Stage II, 86.2%; Stage III, 62.7%). A higher proportion of CR was obtained in patients with tumor of less than 5 cm in diameter than in those with tumors > 5 cm in diameter (82.4% versus 76.3%, respectively; 0.1 > P > 0.05). CR patients enjoyed a marked survival advantage over those with PER, whereas women with SUS demonstrated intermediate 5‐year survival (76.0%, 41.5%, and 7.4%, respectively; P < 0.0001). The same survival gradient of CR > SUS > PER was demonstrated when tumors of each stage were analyzed separately. There was no difference in survival between patients with PER or SUS at 1 month and those with PER or SUS at 3 months. The proportion of recurrent tumors diagnosed as exclusively distant metastases decreased from CR to SUS to PER. Analysis of dosimetry data suggests that the likelihood of CR was not a function of treatment variability. It was concluded that tumors that do not regress promptly are likely to recur, most with distant metastases. Such poor‐prognosis patients should be targeted for early adjuvant or salvage therapy.

Phase I/II study of definitive radiotherapy and chemotherapy (cisplatin and 5-fluorouracil) for advanced or recurrent gynecologic malignancies (preliminary report)

Twenty-three patients with advanced gynecologic malignancy were treated with definitive irradiation and synchronous sensitizing chemotherapy (CT) consisting of cisplatin (CDDP), 50 mg/m2 i.v. rapid infusion, and a 5-day continuous infusion of 5-fluorouracil (5-FU), 750 mg/m2/day. A total of three cycles were administered every 3–4 weeks. Fifteen patients had primary cervical epidermoid carcinoma (three bulky stage IIB, one stage IIIA, ten stage IIIB, one stage IV), four had pelvic recurrences of carcinoma of the cervix, two had endometrial adenocarcinomas (stage IV), and two had vulvar epidermoid carcinoma (one stage III and one stage IV). Radiotherapy (RT) for implantable tumors consisted of 2,000 cGy whole pelvis, 3,000–4,000 cGy split field, and two intracavitary or interstitial insertions, resulting in a total dose of 7,500–8,000 cGy to point A. Three courses of CT were delivered simultaneously with irradiation of the central bulk of tumor: during the first week of whole pelvis RT and with each of the two brachytherapy procedures. Nonimplantable tumors were treated with protracted external beam RT (5,500 cGy tumor dose) and three courses of CT during weeks 1, 4, and 7 of RT. Twenty-one of 23 patients completed RT and 18 of 23 patients completed CT as planned, but half had delays in either RT or CT. Grade 2 or 3 late sequelae consisted of leg edema (one patient), proctosigmoiditis (one patient), bowel obstruction (one patient), vesicovaginal fistula (one patient), and pulmonary embolus (two—one fatal). The incidence of grade 2 and 3 sequelae were 18 and 22%, respectively. With 1–3 years of follow-up evaluation, 12 of 23 (52%) patients are free of disease, and 9 of 22 evaluable patients (41%) have had failure within the pelvis. We conclude that high-dose definitive RT can be delivered with synchronous CDDP and 5-FU at the doses given, with acceptable toxicity. Further study is required to evaluate the impact of radiosensitization on tumor control and late morbidity of therapy. Optimization of irradiation and drug doses as well as the best schedules that may enhance the interaction of these two modalities should be further investigated.

Mullerian adenosarcoma of the cervix with heterologous elements: Diagnostic and therapeutic approach

Mullerian adenosarcoma of the cervix with heterologous elements is an extremely rare tumor first described by Roth and colleagues (L. M. Roth, G. L. Pride, and H. M. Sharma, Cancer 37, 1725-1736) in 1976. Since that time there have been only three subsequent reports of these cervical Mullerian adenosarcomas, which seem to occur most often in the postmenarchal age group. Due to the paucity of cases and the unknown biological potential of the tumor, therapy has ranged from simple excision to radical pelvic surgery and vaginectomy combined with both radiotherapy and chemotherapy. We report another case of Mullerian adenosarcoma of the cervix occurring in a teenage woman and make recommendations about diagnostic and therapeutic measures available to the physician.

Treatment of Carcinoma of the Fallopian Tube Using Cisplatin, Doxorubicin, and Cyclophosphamide

Nine patients with metastatic carcinoma of the fallopian tube were treated with a combination of cisplatin, doxorubicin, and cyclophosphamide. Three are in complete clinical reat 18–56 months following the onset of chemotherapy. Two others died of intercurrent causes without evidence of disease. The remaining four died of tumor at 12, 23, 28, and 52 months following the initiation of treatment. Four second-look laparotomieS were performed upon patients who were in complete clinical remission. No disease was found in any of these patients. It is concluded that this combination is an effective treatment foradenocareinoma of the fallopian tube, and that second-look laparotomy may be useful in assessing respdnse to chemotherapy in this disease.

Mini-colpostats in the treatment of carcinoma of the uterine cervix.

Between 1976 and 1982, 293 patients were treated for carcinoma of the uterine cervix at Washington University by definitive radiotherapy consisting of external beam therapy and two standard Fletcher-Suit applications (tandem plus vaginal colpostats). In ninety-nine patients (34%) mini-colpostats (MC) were used for one or both of their intracavitary insertions while 194 (66%) patients were treated twice with regular Fletcher-Suit colpostats (RC). The frequency of MC use was related to the age and parity of the patients. The distribution by stage of MC and RC groups was not significantly different. Pelvic failure in the MC group was similar to that of the RC group (21% vs 24%). Five-year disease-free survival was also similar between the two groups: 86% vs 80% Stage IB, 57% vs 61% Stage IIA, 47% vs 52% Stage IIB, and 27% vs 45% Stage III for MC and RC groups, respectively. The rate of major complications (grade 3) was 15% in the MC group and 8% in the RC group (p = 0.08). Careful phantom dosimetric studies in both types of colpostats and correlations of dose distributions at various points in the pelvis with frequency of rectal and bladder complications were carried out. The bladder and rectum received a 5-10% higher mean radiation dose (Gy) in the MC group than in the RC group despite lower overall exposure (milligram-hours). Thermoluminescent dosimetry in a polystyrene phantom demonstrates that approximately 10% higher doses are delivered to the bladder, rectum, and point A with an MC system as compared to an RC system, for constant exposure in mgh. Phantom measurements of a newer MC with bladder and rectal shielding demonstrate no influence on the bladder and rectal point dose at a source separation of 3 cm; midline points of the bladder and rectum are not within the full shadow of the shields even if the colpostats are flush with the tandem. Implications for therapy are discussed.

Complications in patients receiving both irradiation and radical hysterectomy for carcinoma of the uterine cervix

One hundred and two patients with invasive carcinoma of the uterine cervix, stages IB, IIA, and selected IA and IIB, were treated using combined radiation therapy and radical hysterectomy. Of these, 88 received approximately 2000 rad of pelvic external radiation and a single 5000-6000 mgh intracavitary implant. Major complications were observed in 5 patients. These resolved spontaneously in 1, and were surgically managed in satisfactory manner in the other 4. Only two of the complications occurred in patients receiving low dose preoperative irradiation. The likelihood of complications was closely related to the radiation dosage. Preoperative radiation prior to radical hysterectomy can be given safely provided that dosimetric principles are observed, and that the radiation and surgical techniques are integrated closely.