Purpose/Objective: To determine the prognostic factors for predicting outcome of patients with adenocarcinoma of the fallopian tube and to evaluate the impact of treatment modalities in managing this uncommon disease.Materials and Methods: A retrospective analysis of the tumor registries from 6 major medical centers from January 1, 1960 up to March 31, 1995 yielded 72 patients with primary adenocarcinoma of the fallopian tube. The Dodson modification of the FIGO surgical staging as it applies to carcinoma of the fallopian tube was utilized. Endpoints for outcome included overall and disease-free survival. Univariate analysis of host, tumor, and treatment factors was performed to determine prognostic significance, and patterns of failure were reviewed.Results: The median age of the study cohort was 61 years (range 30-79 years). Stage distribution was 24 (33%) Stage I; 20 (28%) Stage II; 24 (33%) Stage III; and 4 (6%) Stage IV. Adjuvant chemotherapy was administered to 54 (75%) patients, and postoperative radiotherapy was employed in 22 (31%). In the latter treatment group, 14 (64%) had whole pelvic external beam irradiation, 5 (23%) whole abdominal radiotherapy, 2 (9%) P-32 instillation, and 1 (4%) vaginal brachytherapy alone. Chemotherapy was used in 67% of Stage I and in 79% of Stages II/III/IV disease (not significant); radiotherapy was more commonly employed in Stage I than in Stages II/III/IV (46% vs. 23%, p = 0.05). The 5-, 8-, 15-year overall and disease-free survival for the study patients were 44.7%, 23.8%, 18.8% and 27.3%, 17%, 14%, respectively. Significant prognostic factors of overall survival included Stage I vs. II/III/IV (p = 0.04) and age less than or equal to 60 years vs. >60 years at diagnosis (p = 0.03). Only Stage I vs. II/III/IV (p = 0.05) was predictive of disease-free survival. Patterns of failure included 18% pelvic, 36% upper abdominal, and 19% distant. For all patients, upper abdominal failures were more frequently found in Stages II/III/IV (29%) than in Stage I (7%) (p = 0.03). Relapses solely outside of what would be included in standard whole abdominal radiotherapy portals occurred for only 15% of patients (6 of 40) with failures. Furthermore, patients having any recurrence, including the upper abdomen, were more likely (p = 0.001) to die (45%) than those without any type of relapse (18%).Conclusion: This retrospective, multi-institutional study demonstrated the importance of PICO stage in predicting the overall and disease-free survival of patients with carcinoma of the fallopian tube. Future investigations should consider exploring whole abdominal irradiation as adjunctive therapy, particularly in Stage IT and higher. (C) 1998 Elsevier Science Inc.

The management of patients with gynecological malignancies serves as a prominent example of the importance of multi-modality oncologic therapy. Optimal treatment of these patients requires the skillful implementation of surgery, radiation therapy and chemotherapy. The decision to use simple versus combined modality therapy is crucial and best carried out in centers in which an experienced and coordinated multidisciplinary team is available. In this article, we have reviewed the most recent data regarding the role of radiation therapy in gynecological malignancies and have pointed out those areas where additional confirmatory studies are needed.

Brachytherapy has an established role in the management of a number of malignancies. Contributing to successful application of brachytherapy techniques are proper planning, technical sophistication, and meticulous execution. Equally important, presumably, is proper case selection although conditions favoring brachytherapy utilization are not well described. To facilitate discussion of this topic, a semiquantitative system of brachytherapy case selection is proposed. Variables considered include the natural history of the malignancy, risks involved in the procedure, accessibility of implant site, and results obtainable with other treatment modalities. Brachytherapy Case Selection Scores (0-8) were generated for a number of malignancies. Higher scores were found for sites in which the use of brachytherapy is generally accepted and practiced, implying that the clinical factors considered in this system are clinically relevant, and that such a system could be useful when considering the use of brachytherapy in individual cases. Additional critical analysis regarding brachytherapy case selection is desirable.

OBJECTIVE:To determine the role of irradiation in the management of brain metastases from epithelial ovarian cancer.METHODS:Tumor registries from five university cancer centers were searched to identify ovarian cancer patients with brain metastases. During a 30-year period (1965-1994), 4027 ovarian cancer patients were evaluated, 32 of whom were found to have cerebral metastases. Each received fractionated whole-brain irradiation (median dose 30 Gy, range 20-52.5). Five patients received concomitant chemotherapy with whole-brain irradiation.RESULTS:The median survival time for the whole population was 4 months. For the entire series, symptomatic response (complete response and partial response) was achieved in 23, 16 of whom were palliated until death. Patients with higher Karnofsky performance status (70 or above versus below 70) were more likely to derive a palliative response and attained a statistically significant survival advantage. No other factor predicted the likelihood of deriving a palliative response or a survival advantage after treatment.CONCLUSIONS:In this large review of patients with cerebral metastases from ovarian cancer, we found that most of those treated with whole-brain irradiation achieved palliation until death. Nearly all women with high performance status derived durable palliation from cerebral irradiation. Whole-brain irradiation was an effective means of palliating ovarian cancer metastatic to the brain and provided a favorable alternative to other means of management.

BACKGROUND:Women who do not receive adjuvant irradiation after hysterectomy for endometrial carcinoma (EC) are at risk for developing a pelvic recurrence. Disease- and treatment-related factors were examined for their impact on disease-specific survival (DSS) and pelvic control (PC) in patients with locoregional recurrences to whom salvage radiotherapy was administered. METHODS:Forty-five patients with pelvic/vaginal recurrences of EC were treated at a single institution between 1973 and 1991. The median follow-up period was 89 months. Multiple patient-, disease-, and treatment-related factors were examined with univariate and multivariate analysis for their impact on DSS and PC. Kaplan-Meier methods were used to estimate outcomes. RESULTS:Overall DSS and PC was 51 and 54% at 5 years, respectively. Univariate analysis revealed the following factors to impact on outcome (P < or = 0.05): age (DSS, PC), vaginal stage of recurrence (DSS, PC), size of recurrence (DSS, PC), time interval from hysterectomy (DSS, PC), initial grade (DSS), location of recurrence (PC), and radiation boost technique (PC). CONCLUSION:Women in whom endometrial cancer recurrences develop can be salvaged with aggressive radiotherapy consisting of external beam therapy followed by a radiation boost. Close follow-up after the initial hysterectomy is important because patients with low-volume recurrence limited to the vagina have the best outcome.

BACKGROUND:Positron emission tomography (PET) with labeled fluorodeoxyglucose (FDG) demonstrates increased tracer uptake in many neoplasms. This study was undertaken to define the patterns of FDG uptake in head and neck neoplasms before and after high dose irradiation.METHODS:Twenty-five patients were evaluated prospectively with PET and standard clinical and radiographic techniques before and after irradiation.RESULTS:Twenty-seven primary sites were confirmed pathologically in 23 patients and included the nasopharynx (four lesions), oropharynx (14 lesions), larynx (five lesions), oral cavity (two lesions), and paranasal sinuses (two lesions). Two patients had unknown primary sites. Twenty-four of 27 primary sites correlated with areas of increased tracer uptake on PET scans. Five patients had increased uptake in cervical lymph nodes that were uninvolved by radiographic or clinical criteria. Positron emission tomography seemed to be able to differentiate tumor activity from fluid-filled sinuses in two patients with paranasal sinus tumors. In two patients with unknown primary sites, increased uptake in the base of tongue after PET suggested occult primary sites. Positron emission tomography scans obtained 1 month after high dose irradiation (RT) indicated decreased levels of FDG uptake in all patients' tumors. However, these scans did not accurately reflect the status of disease in these patients. Scans obtained 4 months after RT were believed to assess more accurately the presence of malignancy.CONCLUSIONS:Positron emission tomography is a new modality that may be useful in defining tumor activity in clinically negative areas. Appropriately timed posttreatment PET may be useful in predicting outcome after definitive RT and in distinguishing viable tumors from normal tissue changes after RT in patients with head and neck carcinomas.

PURPOSE:To assess the possible impact of various treatment factors including split-course versus continuous course treatment on the incidence of chronic bowel complications in patients receiving adjuvant pelvic radiotherapy.METHODS AND MATERIALS:A retrospective review was performed of records of 153 patients treated with adjuvant external beam pelvic radiation therapy without brachytherapy for endometrial and colorectal carcinomas. Continuous course radiotherapy was administered in 91 patients (59%) and 62 patients (41%) received split course treatment with a planned 2 week mid-treatment break. Mean pelvic dose and daily fraction size were 51.4 and 1.71 Gray, respectively. Multiple patient and treatment variables were assessed for their possible relationship to chronic bowel complications. Univariate and multivariate statistical analyses were carried out.RESULTS:Twenty-seven patients (18%) developed chronic bowel complications at a median interval of 12 months after radiotherapy. Of all factors analyzed, only the use of split course technique was associated with a significantly higher rate of chronic bowel injury and decreased complication-free survival (p = 0.009).CONCLUSION:This study supports earlier suggestions that the use of split course rather than continuous course pelvic radiotherapy can increase late intestinal complication rates. Possible pathophysiologic mechanisms are discussed.

Thirteen patients with recurrent or new primary gynecologic malignancies after previous radiation therapy (RT) underwent interstitial reirradiation (IRI) from July 1986 through December 1990. Mean and median ages were 63 and 70 years, respectively. Mean and median implanted volumes were 14.3 and 12 cc, respectively. Overall, 9/13 (69%) had complete responses to IRI and 6 (46%) continue to have no evidence of disease (NED) 24-71 months later (median follow-up, 59 months). Of 7 patients with recurrent cervical or new primary vaginal carcinoma, 5 (71%) remain free of disease 27-71 months (median, 58 months) after IRI. Of 6 patients with recurrent endometrial carcinomas, only 1 (16%) continues with NED 24 months after IRI. Patients with NED after IRI had a median disease-free interval prior to IRI of 100 months compared to 6 months in patients failing IRI. Trends toward improved outcomes were observed in squamous vs adenocarcinoma, smaller tumor volumes, higher implant doses, and vaginal wall/suburethra vs vaginal cuff location. One possible complication, a rectovaginal fistula, developed in the presence of recurrent cervical cancer 22 months after IRI. Interstitial reirradiation is an effective treatment for selected patients with recurrent gynecologic malignancies after previous RT. Advantages of IRI over radical surgery include its potential to preserve organ structure and function and its applicability to patients with medical contraindications to salvage surgery. Furthermore, since subsequent exenterative surgery should not be compromised in patients failing IRI, a policy of IRI as initial treatment may be justified for patients in whom the potential for morbidity is limited.

BACKGROUND:This review was done to assess the outcomes and patterns of recurrence in a group of patients with Stage III endometrial carcinoma that might help guide adjuvant therapy.METHODS:A retrospective review was performed of 105 patients treated from 1970-1990 at three institutions. All patients underwent abdominal hysterectomy, with 60 having pathologic node assessment and 45 having cytologic examination of peritoneal washings. A single extrauterine site was involved in 75% of patients; 20% and 5% had two and three sites involved, respectively. All patients received postoperative external beam irradiation to the pelvis or pelvis and paraaortic regions for pathologically positive paraaortic nodes. Actuarial techniques were used to estimate the survival and recurrence rates.RESULTS:The 5-year disease-free survival rate for all patients was 64%. Univariate analysis revealed that the depth of myometrial penetration, the clear cell or papillary serous pathologic type, the histologic grade, and the number of extrauterine sites predicted disease-free survival. Cox regression revealed the grade and pathologic findings to be independent predictors of disease-free survival. The overall 5-year pelvic recurrence rate was 21%, with multivariate analysis revealing the grade to be the strongest prognostic factor. Pathologic findings and the number of involved extrauterine sites were the most important prognostic factors for abdominal recurrence and other sites of distant relapse.CONCLUSIONS:The subgroup of patients with low-grade endometrial tumors or superficial myometrial penetration has a low distant relapse rate. Local control remains the goal of therapy in these patients. Patients with high-grade tumors, deep myometrial penetration, clear cell or papillary serous histologic types, or two or more involved extrauterine sites are at high risk for distant recurrence that may include the abdomen. Investigative strategies delivering aggressive adjuvant therapy are appropriate.

The histogenesis of perianal Paget's disease is controversial. A clinical and pathologic study was done of a patient with a history of adenocarcinoma of the rectum for whom a subsequent diagnosis of perianal Paget's disease was the sole manifestation of recurrent rectal cancer. Immunohistochemical techniques were used to compare and contrast the original rectal adenocarcinoma with the subsequent perianal skin recurrence confined to the epidermis. Both the rectal adenocarcinoma and the Paget's cells were positive for cytokeratin, epithelial membrane antigen, B72.3, and carcinoembryonic antigen and negative for gross cystic disease fluid protein-15, Leu-M1, CA 125, and S-100 protein. These findings, their relevance to the histogenesis of perianal Paget's disease, and the possible clinical implications are discussed.

Radiation therapy, the preferred primary treatment for early squamous cell carcinoma of the glottis, offers high local control rates with voice preservation; however, the optimal treatment schedule is subject to debate. Local control, with and without surgical salvage, and associated long-term effects and complications were retrospectively analyzed in 90 patients treated with definitive radiation therapy for T1-T2 squamous cell carcinoma of the glottis. Patients received three weekly fractions of 333 cGy to a total dose of 60 Gy in 6 weeks. Median follow-up was 51.5 months. With radiation therapy alone, local control was 92% for T1 disease and 88% for T2; with surgical salvage, the control rate was 99%. Long-term effects included moderate hoarseness (16% of patients) and moderate or severe laryngeal edema (10% of patients). In seven patients who underwent salvage surgery, the complication rate was 29%. Despite excellent local control, this regimen may produce more long-term effects and complications than conventional fractionation.

In 1988, the Federation of International Gynecologic Oncologists (FIGO) adopted a new staging system mandating preradiotherapy surgical staging in endometrial cancer. To evaluate the potential impact of this recommendation on patients with cervical involvement (stage II), an analysis of 184 consecutive patients with clinical or pathologic stage II carcinoma of the endometrium treated with definitive intent at three institutions was performed. Median follow-up time was 5.7 years. Treatment consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy with preoperative radiation therapy (RT) (54%), postoperative RT (37%), or both (1%); definitive RT (7%); or radical hysterectomy (1%). The median total RT dose for combined intracavitary and external beam or either alone was 70.6 Gy with a range of 32.4-105.0 Gy. The overall 5-year survival rate and disease-free survival (DFS) rate at 5 years were 70 and 79%, respectively. Of patients treated with surgery and adjuvant radiation, 13% (22/168) had infield pelvic failure (PF) and 18% (31/168) had distant metastases (DM). Patterns of failure in patients receiving preoperative and postoperative radiotherapy are presented. Univariate analysis of pretreatment and treatment factors, including histology, grade, clinical stage, extent of cervical involvement, and timing of adjuvant radiation, revealed histology and grade to be significant predictors of DFS, PF, and DM. Clinical stage was a significant predictor of DFS only in univariate analysis. Multivariate analysis found only histology (P less than 0.001) and grade (P = 0.002) to be predictors of DFS. From this review, we conclude that histology and grade are independent predictors of DFS, and more aggressive treatment should be directed at patients with stage II endometrial cancer found to have high grade adenocarcinoma or papillary serous/clear cell histologic variants. The timing of radiotherapy was not an independent predictor of outcome; therefore, preradiotherapy surgical staging should not impact on DFS and should provide surgicopathologic information to tailor treatment and predict prognosis. The FIGO clinical staging system used in this analysis was not an independent predictor of outcome, and future multivariate analyses will be necessary to test the predictive value on outcome of the new 1988 FIGO surgical staging.

Management of early endometrial carcinoma often consists of surgicopathologic staging followed by adjuvant radiation therapy (RT) for patients at risk of local recurrence. While an intracavitary vaginal cuff boost (VCB) is commonly given after external beam radiation therapy, its effects on local control and complication rates are unknown. To assess these effects, we reviewed 157 patients with FIGO Stage I (n = 134) or incidentally diagnosed (n = 23) endometrial adenocarcinomas. After surgery and external radiation therapy, 103 patients (65.6%) received a vaginal cuff boost of 3000–5000 cGy surface dose (Group I) and 54 (34.4%) did not (Group II). One hundred and two Group I and 52 Group II patients were evaluable for analysis. Median follow-up was 78.0 months for Group I and 60.0 months for Group II. Despite a preponderance of poor prognostic factors in Group II, no significant difference in local failure was seen. A component of local failure was seen in 6 Group I patients (6.0%) and 4 Group II patients (7.7%), p = 0.74. Distant failure, reflecting more advanced disease, was higher in Group II (19.2%) than in Group I(9.0%). Late complications included rectal bleeding/proctitis in 18.6% of Group I patients and 3.8% of Group II patients (p = 0.01). Overall, grade 2 complications occurred in 27.5% and 15.4% of Group I and II patients, respectively (p = 0.09). No difference in frequency of grade 3 complications was evident. Based on this retrospective study, intracavitary vaginal cuff boost after surgery and postoperative external beam radiation therapy does not appear to improve local control in early endometrial adenocarcinoma. Its possible effect on complication rates is uncertain.

The poor outcome of certain patients with Stage III endometrial carcinoma has led some investigators to direct adjuvant therapy to the abdominal cavity. To better define failure patterns, a review of 126 patients with Stage III endometrial carcinoma treated at four institutions was performed. Seventy-four patients were diagnosed at surgery with pathologic Stage III disease, whereas 52 patients presented with clinical Stage III disease. Most patients received external beam irradiation to the pelvis with a variety of boost techniques. Site of disease, grade, depth of invasion, and pathology were examined for prognostic significance. Actuarial techniques were used to analyze survival and recurrences. For the 52 clinical Stage III patients, 5-year survival was 36%. The median survival of 20 patients who were treated with radiation therapy (RT) following biopsy was 9 months. Pelvic control was poor in these patients, with 16/18 evaluable patients failing locally. Thirty-two patients who underwent resection with adjunctive RT had a 5-year survival of 48%. Local failure occurred in 40% of patients, whereas 38% of patients had abdominal failure. Isolated abdominal failure was infrequent with 6% failing as isolated recurrence, and 16% failing as the only site of distant disease. For 74 pathologic Stage III patients, 5-year survival was 54%. Local failure resulted in 20% of patients, and isolated abdominal failure occurred in 7% of patients. The subset of patients with ovarian or tubal involvement included 42 patients, with a 5-year survival of 60%. Further analysis of this subset by grade and depth of myometrial penetration was found to be prognostically significant. Twenty-four patients who were Stage III because of parametrial or pelvic peritoneal involvement had a 5-year survival of 44%. Local control and survival is improved in Stage III patients treated with surgical resection. The high rate of distant metastases in both abdominal and extra-abdominal sites has significant therapeutic implications.

Spinal cord compression as a consequence of mass lesions due to extramedullary hematopoiesis is a well-described but rare syndrome occurring in thalassemia and some other hematologic conditions. After low-dose radiotherapy alone, a rapid and durable response occurred in a patient with thalassemia. No side effects were encountered and the patient has been stable neurologically for over 7 years since treatment. The results of the current case, and those previously reported in which radiotherapy alone was given, suggest that low-dose radiotherapy should be considered as a primary treatment modality for the management of this syndrome, at least in patients with thalassemia.