Ming-Shian Kao

Effect of tumor size on the prognosis of carcinoma of the uterine cervix treated with irradiation alone

The authors conducted a retrospective analysis of 1178 patients with histologically proven invasive carcinoma of the uterine cervix treated with irradiation alone. The minimum follow‐up time was 3 years. The 10‐year actuarial pelvic failure rate in Stage IB was 6% for tumors less than 3 cm, 15% for tumors 3 to 5 cm, and 30% for tumors more than 5 cm (P = 0.0018). The 10‐year actuarial pelvic failure rate in Stage IIA was 10% for tumors less than 3 cm, 28% for tumors 3 to 5 cm, and 20% for tumors more than 5 cm (P = 0.09). Stage IIB unilateral nonbulky tumors (less than 5 cm) had a 20% pelvic failure rate compared with 28% for bilateral lesions and 35% for unilateral bulky tumors (more than 5 cm) (P = 0.35). In Stage IIB, pelvic failures were greater when disease extended into the lateral parametrium (30%) compared with medial parametrial involvement only (17%) (P = 0.01). In Stage III unilateral nonbulky tumors, the pelvic failure rate was 28% compared with 45% to 50% for unilateral bulky lesions (P = 0.002). Bilateral parametrial disease in Stage IIB did not increase the pelvic failure rate (21% in both subgroups) (P = 0.83), whereas in Stage III, bilateral parametrial involvement was associated with a 48% pelvic failure rate versus 28% for unilateral extension (P ≤ 0.01). Five‐year disease‐free survival (DFS) rates for IB tumors less than or equal to 3 cm was 90% versus 67% for tumors more than 3 cm (P = 0.01). In Stage IIA tumors less than or equal to 3 cm, 5‐year DFS was 70% versus 45% for tumors more than 3 cm. Patients with Stage IIB nonbulky tumors (less than or equal to 5 cm in diameter) had better 10‐year DFS (65% to 70%) compared with those with bilateral bulky tumors (45% to 55%) (P = 0.10). Stage I11 patients with unilateral nonbulky tumors had a 55% 10‐year DFS compared with 35% to 40% for bulky tumors or bilateral parametrial involvement (P = 0.002). The authors concluded that clinical stage and size of tumor are critical factors in the prognosis, therapy selection, and evaluation of results in carcinoma of the uterine cervix.

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.

Impact of dose in outcome of irradiation alone in carcinoma of the uterine cervix: analysis of two different methods

This is a retrospective analysis of 1211 patients with histologically proven invasive carcinoma of the uterine cervix with a minimum follow-up of 3 years treated with irradiation alone. The pelvic failure rates by stage were 9.6% for IB, 18.6% for IIA, 23% for IIB, 41% for III, and 75% for Stage IVA disease. External beam and intracavitary irradiation doses to point A and pelvic lymph nodes were calculated. In patients with Stage IB and IIA disease there was no significant correlation between doses to these points and pelvic tumor control. In Stage IIB doses of less than 6000 cGy to point A correlated with a high pelvic failure rate (8 of 12, 66.7%) in contrast to doses of 6000 to 9000 cGy (61 of 261, 23.4%) or higher than 9000 cGy (10 of 74, 13.5%) (p less than or equal to 0.01). In Stage III the pelvic failure rate with doses below 6000 cGy to point A was 72% (18 of 25) compared to 39% (71 of 180) for 6000 to 9000 cGy or 35% (27 of 77) with doses above 9000 cGy (p less than or equal to 0.01). TDF calculation of doses was carried out. In Stage IB and IIA there was no significant correlation between TDF to point A and probability of pelvic recurrence. In Stage IIB with TDF below 135, the pelvic recurrence rate was 41.6% (20 of 48) compared to 20% (61 of 305) with higher TDF (p less than or equal to 0.01). In Stage III the pelvic failure rate was 51% with TDF below 160 (70 of 136) in comparison with 29.5% (46 of 156) with higher TDF (p less than or equal to 0.01). Grade 2 sequelae of therapy were noted in about 10% of the patients and grade 3 in 4.7% of patients with Stage IB (18 of 384), 10.2% (12 of 128) with Stage IIA, 9.3% (33 of 353) with Stage IIB, and 8.2% (24 of 293) with Stage III disease. Doses from external beam and intracavitary irradiation to the rectum or the bladder neck were calculated. The actuarial incidence of major rectal or rectosigmoid sequelae was 2% to 4% with doses to the rectum of 6000 to 8000 cGy, 7% to 8% with 8000 to 9500 cGy, and 13% with doses higher than 9500 cGy (p less than or equal to 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of pelvic tumor control and impact on survival in carcinoma of the uterine cervix treated with radiation therapy alone.

A total of 1054 patients with histologically confirmed invasive carcinoma of the uterine cervix were treated with radiation therapy alone between 1959 and 1982. All patients are available for a minimum of 3 years follow-up. Radiation therapy consisted of external irradiation to the whole pelvis (1000-2000 cGy) and parametria (for a total of 4000-6000 cGy) combined with two intracavitary radioactive source insertions (6000-7500 cGy to point A). Patients with Stage IIB, III, and IVA have been consistently treated with somewhat higher doses of external irradiation and intracavitary insertions. A small group of 54 patients with Stage IIB or IIIB had pelvic lymphadenectomy following the irradiation (1960-1964). There was a strong correlation between the tumor regression within 30 days from completion of radiotherapy and the incidence of pelvic recurrences or distant metastases for each of the anatomical stages. The 10-year survival rate for Stage IB was 76%, Stage IIA 60%, Stage IIB 45%, and Stage III 25%. Many of the deaths were due to intercurrent disease. Thus, the 10-year tumor-free survival was 80% for Stage IB, 60% for Stages IIA and IIB and 35% for Stage III. In Stage IB total doses of 6000 cGy or higher to point A resulted in 94% pelvic tumor control. In Stage IIA, the pelvic tumor control was 87% with doses of 6000 cGy to point A or higher. However, in Stage IIB the pelvic tumor control was 58% with doses below 6000 cGy, 78% with 6001-7500 cGy and 82% with higher doses. In Stage IIIB the pelvic tumor control was 42% with doses below 6000 cGy, 57% with 6001-7500 cGy and 68% with higher doses. Tumor control in the pelvis was correlated with the following 5 year survivals: Stage IB-95% (353 patients); Stage IIA-84% (116 patients); Stage IIB-84% (308 patients); Stage IIIB-74% (245 patients). The 5-year survival for patients that recurred in the pelvis was 30% for Stage IB, about 15% for Stages IIA-B and only 5% in Stage III. Patients with tumor control in the pelvis had a significantly lower incidence of distant metastases than patients who initially failed in the pelvis (9.3% vs. 58.6% in Stage IB, 21.6% vs 52.6% in Stage IIA, 19.8% vs 16.7% in Stage IIB, and 31.2% vs 50% in Stage III). In Stage IIB the figures were 19.8% and 16.7% because the initial pelvic recurrence was frequently concurrent with distant metastases.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical stage I endometrial cancer : prognostic factors for local control and distant metastasis and implications of the new figo surgical staging system

A retrospective analysis is reported in 858 patients with clinical Stage I carcinoma of the endometrium treated definitively with combined irradiation and total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO) from January 1960 through December 1986. Most patients received a preoperative intracavitary insertion (3500-4000 mgh to the uterus and a 6500 cGy surface dose to the upper vagina) followed by a TAH-BSO within 1-2 weeks. Some patients received postoperative external beam irradiation (2000 cGy whole pelvis and an additional 3000 cGy to the parametria, with a midline stepwedge) when factors such as deep myometrial invasion were present. Occasionally patients were treated with a preoperative intracavitary insertion and preoperative external beam irradiation (2000 cGy whole pelvis). The 5-year progression-free survivals by FIGO (1988) surgical stage were 93% for IA, 90% for IB, and 91% for Stage IC. An analysis of multiple variables was performed to ascertain their prognostic significance. Factors that significantly affected the 5-year progression-free survivals by univariate analysis were grade (grade 1 = 95%, grade 2 = 88%, grade 3 = 73%; p less than 0.0001), histology (adenoacanthoma = 96%, clear cell = 89%, adenocarcinoma = 89%, papillary = 81%, adenosquamous = 80%; p = 0.04), lower uterine segment involvement (uninvolved = 89%, involved = 73%; p = 0.006), depth of myometrial invasion (no residual tumor = 91%, limited to the endometrium = 96%, less than 1/3 myometrial penetration = 92%, 1/3 - 2/3 = 100%, greater than 2/3 = 50%; p = 0.02), peritoneal cytology (negative = 92%, positive = 56%, p less than 0.0001), uterine serosal involvement (uninvolved = 89%, involved = 55%; p less than 0.0001), vascular space invasion (absent = 89%, present = 75%; p = 0.001), and the presence of extrauterine disease (absent = 90%, present = 64%; p less than 0.0001). A multivariate analysis of these prognostic variables showed that histological grade (p = 0.001), peritoneal cytology (p = 0.004), and uterine serosal involvement were prognostic for local failure and that peritoneal cytology (p less than 0.001), grade (p = 0.001), age (p = 0.002), and extrauterine disease (p = 0.02) were prognostic for the development of distant metastasis.

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.

Radiation therapy alone or combined with surgery in the treatment of barrel-shaped carcinoma of the uterine cervix (stages IB, IIA, IIB)

This retrospective analysis reports the results of therapy in 128 patients with carcinoma of the uterine cervix classified as barrel-shaped or expanded cervix (over 5 cm in diameter). Seventy-five percent of the patients were treated with irradiation alone and 25% with combinations of irradiation and surgery. The results of therapy are compared with those observed in 714 patients with non-barrel-shaped carcinoma of the uterine cervix treated with similar techniques during the same period of time. The distribution of histological type of tumor was similar in both groups (90% epidermoid carcinoma, 8% adenocarcinoma, and 2% adenosquamous carcinoma). Approximately 15% of the patients in both groups with Stage IB and 25% with Stage IIA and IIB had positive endometrial curettings (stromal invasion or replacement by tumor only). Thus, the aggressive behavior observed in the barrel-shaped tumors is not a result of endometrial involvement, but to the large volume of tumor present. The actuarial 5-year tumor free survival in Stage IB barrel-shaped cervix was 76% compared to 92% in the non-barrel-shaped lesions. In Stage IIA the 5-year NED survival for patients with barrel-shaped cervix was 60 compared to 80% for the patients with non-barrel-shaped cervix. In Stage IIB the survival rates were 58 and 70%, respectively. A noteworthy finding in this analysis is the high incidence of distant metastases in the patients with barrel-shaped cervix (32% in Stage IB, 40% in Stage IIA, and 32% in Stage IIB) in comparison with patients with non-barrel-shaped tumors (10% in Stage IB, 16% in Stage IIA, and 25% in Stage IIB). The incidence of pelvic failures was comparable in both groups. Higher doses of irradiation resulted in better tumor control, which was comparable to that observed with a combination of irradiation and surgery (conservative hysterectomy). The 5-year survival rate in Stage IB was similar in both the barrel-shaped and non-barrel-shaped tumors treated with irradiation alone or combination irradiation and surgery. In Stage IIA the non-barrel-shaped lesions had the same survival with either treatment technique. In the barrel-shape group, eight patients treated with irradiation alone or survival of 70%, compared to 45% in 24 patients treated with irradiation alone. However, these differences are not statistically significant (p = .50). In eight patients treated with definitive irradiation and a lymphadenectomy and four patients irradiated after an exploratory laparotomy, two major and three minor (grade 2) complications were noted.(ABSTRACT TRUNCATED AT 400 WORDS)

Outcome of recurrent cervical carcinoma following definitive irradiation

This report is a retrospective analysis of 376 patients with recurrent cervical carcinoma, following definitive radiation therapy to 1054 patients with stage IB-IVA carcinoma of the uterine cervix treated at the Radiation Oncology Center, Mallinckrodt Institute of Radiology, from January 1959 through December 1982. The sites of failure after treatment by stage at initial diagnosis were classified as pelvic only (P), pelvic plus distant metastasis (P + DM), or distant metastasis only (DM). The sites of first failure were for stage IB, P = 0.8%, P + DM = 7.4%, DM = 7.9%; for stage IIA, P = 1.7%, P + DM = 14.7%, DM = 17.2%; for stage IIB, P = 10.4%, P + DM = 11.0%, DM = 14.9%; for stage III, P = 15.4%, P + DM = 23.9%, DM = 18.9%; and for stage IV, P = 16.7%, P + DM = 61.1%, DM = 16.7%. The actuarial probability of pelvic failure at 5 years from initial therapy was 8% for stage IB, 16% for stage IIA, 21% for stage IIB, 42% for stage III, and 100% for stage IV. The incidence of distant metastasis at 5 years was 14, 32, 28, 47, and 100% for stages IB, IIA, IIB, III, and IV, respectively. The therapy after failure was surgery, irradiation, irradiation plus surgery, or chemotherapy. There appeared to be no major difference in survival after recurrence by type of treatment or initial stage. The overall survival at 5 years for all untreated patients was 1%. The median survival was evaluated as a function of time to failure after initial treatment. Patients who developed disease more than 36 months after initial treatment had a median survival of 22.5 months. The median survival was 12.1, 7.6, 9.4, and 9.1 months for those failing less than 6, 6-12, 13-24, and 25-36 months after initial treatment. Severe treatment complications occurred in 3.6% (5/140).

Radiation therapy in management of carcinoma of the vulva with emphasis on conservation therapy

Background. This report consists of a retrospective analysis of 50 patients with primary invasive and 17 with recurrent histologically confirmed vulvar carcinoma treated with radiation therapy for locoregional disease.

Results of therapy, analysis of failures, and prognostic factors for clinical and pathologic stage III adenocarcinoma of the endometrium

A retrospective analysis was performed on 427 patients with clinical stage I, II, and III adenocarcinoma of the endometrium treated definitively with total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO) and pre- or postoperative irradiation at our institution from January 1960 through December 1981. Of 310 patients with clinical stage I, 21 (6.8%) and 9 of 90 (10%) clinical stage II patients were found to have pathologic stage III (CS I-II/PS III) tumors. In addition, 27 patients had clinical stage III (CS III) tumors at the time of diagnosis. At 5 years the overall and disease-free survival for all patients with clinical and/or pathologic stage III disease was 43.5 and 46.2%, respectively. The 5-year disease-free survival for CS I/PS III was 67.3% compared to 32.6% for CS II/PS III and 33.4% for CS III. Failure to control the disease in the pelvis occurred in 14.3% of the CS I/PS III patients and in 44.4 and 33.3% of the CS II/PS III and CS III patients, respectively. The appearance of distant metastasis was higher with increasing stage (19.1% for CS I/PS III, 33.3% for CS II/PS III, and 48.1% for CS III). Eighty percent of all failures occurred within 40 months. Grade of the tumor was associated with increasing pathologic stage but not with ability to control the disease in the pelvis. However, there was a tendency for higher grade lesions to fail more often at distant sites.