Ureteroarterial fistulas after radical pelvic surgery: pathogenesis, diagnosis, and therapeutic modalities.

Ureteroarterial fistulas (UAF) are a rare but potentially life-threatening complication of intra-abdominal malignancy, typically occurring after vascular or pelvic surgery. Patients with a history of radical pelvic surgery, chronic indwelling ureteral stents, and prior pelvic radiation appear to be at increased risk. The predisposing risk factors suggest that gynecological oncologists are the likely specialty to face this problem and should be familiar with the clinical presentation and etiology of UAF. We present two such cases to illustrate these salient points of clinical diagnosis and management.

Effective palliative radiation therapy in advanced and recurrent ovarian carcinoma.

PURPOSE: To retrospectively review our experience using radiation therapy as a palliative treatment in ovarian carcinoma. METHODS AND MATERIALS: Eighty patients who received radiation therapy for ovarian carcinoma between 1983 and 1998 were reviewed. The indications for radiation therapy, radiation therapy techniques, details, tolerance, and response were recorded. A complete response required complete resolution of the patient's symptoms, radiographic findings, palpable mass, or CA-125 level. A partial response required at least 50% resolution of these parameters. The actuarial survival rates from initial diagnosis and from the completion of radiation therapy were calculated. RESULTS: The median age of the patients was 67 years (range 26 to 90 years). A median of one laparotomy was performed before irradiation. Zero to 20 cycles of a platinum-based chemotherapy regimen were delivered before irradiation (median = 6 cycles). The reasons for palliative treatment were: pain (n = 22), mass (n = 23), obstruction of ureter, rectum, esophagus, or stomach (n = 12), a positive second-look laparotomy (n = 9), ascites (n = 8), vaginal bleeding (n = 6), rectal bleeding (n = 1), lymphedema (n = 3), skin involvement (n = 1), or brain metastases with symptoms (n = 11). Some patients received treatment for more than one indication. Treatment was directed to the abdomen or pelvis in 64 patients, to the brain in 11, and to other sites in 5. The overall response rate was 73%. Twenty-eight percent of the patients experienced a complete response of their symptoms, palpable mass, and/or CA-125 level. Forty-five percent had a partial response. Only 11% suffered progressive disease during therapy that required discontinuation of the treatment. Sixteen percent had stable disease. The duration of the responses and stable disease lasted until death except in 10 patients who experienced recurrence of their symptoms between 1 and 21 months (median = 9 months). The 1-, 2-, 3-, and 5-year actuarial survival rates from diagnosis were 89%, 73%, 42%, and 33%, respectively. The survival rates calculated from the completion of radiotherapy were 39%, 27%, 13%, and 10%, respectively. Five percent of patients experienced Grade 3 diarrhea, vomiting, myelosuppression, or fatigue. Fourteen percent of patients experienced Grade 1 or 2 diarrhea, 19% experienced Grade 1 or 2 nausea and vomiting, and 11% had Grade 1 or 2 myelosuppression. CONCLUSIONS: In this series of radiation therapy for advanced ovarian carcinoma, the response, survival, and tolerance rates compare favorably to those reported for current second- and third-line chemotherapy regimens. Cooperative groups should consider evaluating prospectively the use of radiation therapy before nonplatinum and/or nonpaclitaxel chemotherapy in these patients.

Mandibular metastasis in a patient with endometrial cancer.

Gynecologic cancers metastatic to bone are a rare entity, and a metastasis to the mandible at initial presentation is even more infrequently seen. We present a case of a 71-year-old woman with stage IV endometrial cancer with a metastasis to the mandible, with no other sites of distal spread apparent. The endometrial tumor was a FIGO grade III adenocarcinoma. The pathologic evaluation of the mandibular lesion revealed poorly differentiated adenocarcinoma with focal squamous differentiation. She was treated with a total abdominal hysterectomy and bilateral salpingo-oophorectomy, radiation therapy to the mandible, and chemotherapy consisting of Taxol and carboplatin for six cycles. She had a complete response, but 10 months after the original diagnosis developed spinal cord compression and progressive disease in the pelvis. Patients in good clinical condition with a single bone metastasis should be treated aggressively, as survival can be extended.

Small-cell lung carcinoma: an analysis of 194 consecutive patients.

The treatment of small-cell lung carcinoma (SCLC) requires the careful combination of chemotherapy and radiation therapy. To understand the factors involved in the outcome of these patients, the authors undertook a study of patients treated for limited stage SCLC. The charts of 194 consecutive patients treated at our facilities between 1986 and 1994 were reviewed. All patients underwent thoracic radiation therapy (TRT), 50% received prophylactic cranial irradiation (PCI), and all but one received chemotherapy. The probability of survival at 5 years was 14%, and the disease-free survival (DFS) was 17%. Patients receiving a combination of platinum and etoposide (PE) and Cytoxan (Bristol-Myers, Evansville, IN, U.S.A.), Adriamycin (Adria Laboratories, Dublin, OH, U.S.A.), and Vincristine (Eli Lilly, Indianapolis, IN, U.S.A.) (CAV) experienced a DFS at 3 years of 31%, versus 14% for CAV only and 18% for PE only (p = 0.004). In a multivariate survival analysis, only PCI (p = 0.001), having received PE and CAV (p = 0.01), and response to treatment (p = 0.001) were significant. Radiation dose and field size did not influence outcome. The combination of PE and CAV chemotherapy produced the best results in our series. Unanswered questions regarding the optimal TRT dose, field size, and timing of TRT await the results of ongoing randomized trials.

Small cell anaplastic carcinoma of the prostate: seven new cases, review of the literature, and discussion of a therapeutic strategy.

Small cell anaplastic carcinoma of the prostate (SCCP) is a rare entity; a literature review disclosed fewer than 150 cases. SCCP has an aggressive course, and both local and distant failure is common. The optimal treatment method has not been clearly established. We review our experience with 7 patients, with attention paid to clinical and pathological details based on a review of the histological specimens. Three patients had mixed tumors of both SCCP and adenocarcinoma, 3 had pure adenocarcinomas that recurred as small cell, and 1 had pure small cell. Our series confirms the aggressive nature of the disease, with all patients dying of their disease < or = 42 months after diagnosis. All patients progressed locally, and at least 5 later developed distant metastases. Treatment with combination chemotherapy and/or hormones resulted in short-lived responses in most patients. We recommend use of hormonal manipulation and combination chemotherapy as well as surgery and/or radiation therapy to the prostate for local control and emphasize that histologic recognition of the entity is important for proper treatment.

Low doses of prophylactic cranial irradiation effective in limited stage small cell carcinoma of the lung.

PURPOSE: Prophylactic cranial irradiation (PCI) for the prevention of brain metastasis in small cell lung cancer remains controversial, both in terms of efficacy and the optimal dose-fractionation scheme. We performed this study to evaluate the efficacy of PCI at low doses. METHODS AND MATERIALS: One hundred and ninety-seven patients were referred to our institution for treatment of limited stage small cell carcinoma of the lung between June 1986 and December 1992. Follow-up ranged from 1.1 to 89.8 months, with a mean of 19 months. Eighty-five patients received PCI. RESULTS: Patients receiving PCI exhibited brain failure in 15%, while 38% of untreated patients developed metastases. This degree of prophylaxis was achieved with a median total dose of 25.20 Gy and a median fraction size of 1.80 Gy. At these doses, acute and late complications were minimal. Patients receiving PCI had significantly better 1-year and 2-year overall survivals (68% and 46% vs. 33% and 13%). However, patients with a complete response (CR) to chemotherapy and better Karnofsky performance status (KPS) were overrepresented in the PCI group. In an attempt to compare similar patients in both groups (PCI vs. no PCI), only patients with KPS > or = 80, CR or near-CR to chemotherapy, and treatment with attempt to cure, were compared. In this good prognostic group, survival was still better in the PCI group (p = 0.0018). CONCLUSION: In this patient population, relatively low doses of PCI have accomplished a significant reduction in the incidence of brain metastasis with little toxicity. Whether such treatment truly improves survival awaits the results of additional prospective randomized trials.

Radiation and chemotherapy. Treatment of localized pancreatic carcinoma.

Patients unable to undergo a pancreatoduodenectomy for adenocarcinoma of the pancreas are often treated with radiation therapy. A randomized trial by the Gastrointestinal Tumor Study Group has shown an advantage in combining it with chemotherapy. A similar size retrospective study at a large community radiation therapy center assessed this finding in the nonprotocol setting. The study population consisted of 86 patients treated with primary radiation therapy between 1982 and 1992; 62 of them also received chemotherapy. The overall probability of survival was 39% and 13% at 12 and 24 months respectively. Patients receiving chemotherapy had a significantly (p = .018) longer survival (44% versus 25% at 12 months). Results confirm the Study Group's findings and suggest that they be applied to the community setting.

Local control in medically inoperable lung cancer: an analysis of its importance in outcome and factors determining the probability of tumor eradication.

PURPOSE: For patients who are medically unable to tolerate a surgical resection for technically resectable non-small-cell lung carcinoma, radiation therapy is an acceptable alternative. We report on the effect of achieving local control of the primary tumor on survival end-points, and analyze factors that may influence local control. METHODS AND MATERIALS: We reviewed the records of 152 patients with medically inoperable non-small-cell lung carcinoma treated at our institutions. All patients had technically resectable lesions and no evidence of metastatic disease. Treatment was delivered using megavoltage irradiation to doses ranging from 45 to 75 Gy. RESULTS: For patients with tumors 3 cm or less, locally controlling the tumor significantly improved survival (p = .0371). Patients with T1 tumors had a higher probability of survival and disease-free-survival than patients with larger tumors if the primary tumor was locally controlled, but this survival advantage disappeared if the tumor was not controlled. Overall, patients with smaller tumors had a lower incidence of distant spread, but this association was maintained only when the primary tumor was controlled (36 month risk of 10%, 23%, and 57% for tumors < 3 cm, 3-4.9 cm, 5 cm or greater, respectively, p = .0027). For patients whose tumors were not controlled, there was no significant difference in the risk of distant dissemination by tumor size. Higher radiation doses influenced local control and metastatic spread. We observed no influence of the initial field size in the risk of local control and in the probability of survival. CONCLUSION: Radical radiation therapy is an effective treatment for small (T1 or < 3 cm) tumors when treated to doses of 65 Gy or more, and should be offered as an alternative to surgery in elderly or infirm patients. New therapeutic strategies to improve the local control rate should be considered for larger tumors, through the use of hyperfractionated treatment, endobronchial "boost" irradiation, and sensitizing chemotherapy agents.

Prevention of heterotopic bone formation with low dose radiation therapy.

Radiation therapy to control heterotopic bone formation does not appear to be commonly used in sites other than hips where effective control is evident following arthroplasty. Reported are the results in 12 sites in 10 patients including three with treatment to the elbow, humerus, and ulna. Ten sites received a radiation dose of 10.00 Gy, one 16.00 Gy, and one was treated to 20.00 Gy, all delivered in 2.00 Gy fractions. Preoperative and follow-up x-rays were reviewed and graded. There was no clinically significant regrowth of heterotopic bone. Five sites (42%) demonstrated mild regrowth or persistence following surgery with the other seven (58%) showing no evidence of heterotopic bone. No complications were seen. Radiation therapy is effective for the prevention of heterotopic bone after total hip arthroplasties as well as surgery for fractures to other areas.

Radiation therapy in the management of medically inoperable carcinoma of the lung: results and implications for future treatment strategies.

Surgery is the treatment of choice for resectable non-small cell lung carcinoma. For patients who are medically unable to tolerate a surgical resection or who refuse surgery, radiation therapy is an acceptable alternative. We reviewed the records of 152 patients with medically inoperable non-small cell lung carcinoma treated at our institution between 1982 and 1990. Patients with metastatic disease, mediastinal lymph node involvement or unresectable tumors were excluded. The actuarial overall survival at 2 and 5 years was 40% and 10%, respectively. The disease-free survival at 2 and 5 years was 31% and 15%. The disease-free survival for patients with T1 tumors was 55% at 2 years, versus 20 and 25% for T2 and T3 lesions, respectively (p = .0006). Increasing tumor dose was also associated with increasing disease-free survival (p = .0143). Overall, 66% percent of the patients were considered to have failed. Of these, 70% showed a component of local failure and 45% failed distantly. Patients with T1 tumors experienced a lower probability of failing locally or distantly than did patients with T2 or T3 tumors. A reduced risk of local and distant failure was seen for patients treated to doses of greater than 65 Gray, especially for T1 tumors. We conclude that radical radiation therapy is an effective treatment for small tumors when treated to doses of 65 Gray or more. Since local failure is the prominent pattern of relapse in patients with large tumors, new therapeutic strategies should be considered for this patient group.

Prognostic variables in the treatment of squamous cell carcinoma of the vulva.

Records of 98 patients undergoing surgery for squamous cell carcinoma of the vulva between 1960 and 1982 were analyzed to evaluate and develop treatment policy. There were 32, 34, 26, and 6 patients in FIGO stages I-IV, respectively. Eighty-six patients underwent radical vulvectomy, 8 patients underwent less extensive procedures, and 4 underwent more extensive procedures. Eighty-seven patients underwent inguinal node dissection, and 40 underwent pelvic node dissection as well. Eight patients received external beam irradiation. Actuarial 5-year survival was 57%. Age, tumor size, FIGO (clinical) stage, surgically determined T and N stages, tumor differentiation, lymph vessel invasion, extent of surgical procedure, and adjuvant irradiation were analyzed to determine their effects on local control, freedom from distant metastases, and survival, using single variable and multivariate analysis. Local control was significantly related to FIGO stage; freedom from distant metastasis was significantly related to surgical N stage, tumor size, and surgical T stage; survival was significantly related to surgical N stage, tumor size, surgical T stage, age, and lymph vessel invasion. Metastatic involvement of inguinal lymph nodes was significantly correlated with tumor size and differentiation. Of 87 evaluable patients, 33 had inguinal node involvement, and of these, 17 developed recurrent disease. All 7 patients with pelvic node metastases had positive inguinal nodes, and all died; the cause of death could be determined in 5, of whom 4 manifested distant metastases. Pelvic lymphadenectomy conferred no survival benefit in this series, even in the presence of positive inguinal nodes. Local vulvar recurrence is a significant problem in patients with positive inguinal nodes, and postoperative irradiation should be directed to this area in these patients. Patients with vulvar recurrences, especially those occurring at least 2 years after surgery, can be successfully salvaged, and should therefore be treated aggressively.

Pure seminoma of the testis: the results of radiation therapy in patients with elevated human chorionic gonadotropin titers.

The management and prognosis of human chorionic gonadotropin-producing seminoma still are controversial issues. In a review of 210 patients irradiated between 1950 and 1982, 10 had elevated human chorionic gonadotropin values: 3 with stage I, 6 with stage II and 1 with stage IV disease. All human chorionic gonadotropin values became negative: 4 postoperatively and 6 following radiotherapy. All patients are well with a mean followup of 6 years. One patient who suffered liver metastases only was salvaged by chemotherapy. Based on these patients human chorionic gonadotropin production is not an unfavorable prognostic sign in cases of pure seminoma.

Variation in the lung inhomogeneity correction factor with beam energy. Clinical implications.

In order to determine the magnitude of the dosimetry error introduced by failing to correct for increased transmission through lung tissue in treating thoracic malignancies, measurements in a phantom were taken using different field sizes, inhomogeneity thicknesses and photon qualities. The results indicate that the error introduced by neglecting the inhomogeneity correction is greatest at lower photon energies, smaller field sizes and greater thickness of inhomogeneity. Correction factors to account for the lung inhomogeneity were obtained from phantom measurements and were compared with those calculated using the tissue-air ratio and Batho-Young algorithms; correlation coefficients describing the relationship between measured and calculated values exceeded 0.995. The calculated values tended to overestimate the correction factor and differed most from the measured correction factors at lower energies, smaller field sizes, and greater inhomogeneity thicknesses. The importance of these results in clinical radiation therapy is discussed.

Validation of the tumor, nodes and metastasis classification of renal cell carcinoma.

A retrospective analysis of 252 patients with renal cell carcinoma was performed with the tumor, nodes and metastasis system of cancer staging. Each patient received a clinical and a pathological classification. Patient survival was calculated for each pT stage. All patients with stage pT1 disease (100 per cent) were alive at 5 years, as were 91 per cent of those with stage pT2 tumors. Higher T stages showed poorer survival; 58 per cent of the patients with stage pT3 and only 25 per cent with stage pT4 tumors were alive at 5 years. Invasion into the inferior vena cava (pT3c) had an adverse effect on survival, which was statistically significant compared to patients in the pT3a and pT3b subgroups. The type of surgical procedure performed had no influence on ultimate survival, nor did the use of adjuvant radiation therapy. The tumor, nodes and metastasis system clearly documents that the survival of patients with renal cell carcinoma depends on the local extent of the primary tumor, determined at the time of surgical exploration.

Meningioma: analysis of recurrence and progression following neurosurgical resection.

The rates of survival, tumor recurrence, and tumor progression were analyzed in 225 patients with meningioma who underwent surgery as the only treatment modality between 1962 and 1980. Patients were considered to have a recurrence if their studies verified a mass effect in spite of a complete surgical removal, whereas they were defined as having progression if, after a subtotal excision, there was clear radiological documentation of an increase in the size of their tumor. There were 168 females and 57 males (a ratio of 2.9:1), with a peak incidence of tumor occurrence in the fifth (23%), sixth (29%), and seventh (23%) decades of life. Anatomical locations were the convexity (21%), parasagittal area (17%), sphenoid ridge (16%), posterior fossa (14%), parasellar region (12%), olfactory groove (10%), spine (8%), and orbit (2%). The absolute 5-, 10-, and 15-year survival rates were 83%, 77%, and 69%, respectively. Following a total resection, the recurrence-free rate at 5, 10, and 15 years was 93%, 80%, and 68%, respectively, at all sites. In contrast, after a subtotal resection, the progression-free rate was only 63%, 45%, and 9% during the same period (p less than 0.0001). The probability of having a second operation following a total excision after 5, 10, and 15 years was 6%, 15%, and 20%, whereas after a subtotal excision the probability was 25%, 44%, and 84%, respectively (p less than 0.0001). Tumor sites associated with a high percentage of total excisions had a low recurrence/progression rate. For example, 96% of convexity meningiomas were removed in toto, and the recurrence/progression rate at 5 years was only 3%. Parasellar meningiomas, with a 57% total excision rate, had a 5-year probability of recurrence/progression of 19%. Only 28% of sphenoid ridge meningiomas a second resection, the probability of a third operation at 5 and 10 years was 42% and 56%, respectively. There was no difference in the recurrence/progression rates according to the patients' age or sex, or the duration of symptoms. Implications for the potential role of adjunctive medical therapy or radiation therapy for meningiomas are discussed.

Adjuvant postoperative radiotherapy in carcinoma of the rectum and rectosigmoid.

Local recurrence occurs in 30% to 50% of rectal cancer patients treated with surgery alone if there is tumor extension beyond the bowel wall alone or in conjunction with nodal involvement. This analysis is of 97 such patients who received postoperative irradiation (XRT) in prospective and standardized fashion at Massachusetts General Hospital (MGH) (4500 rad in 25 fractions to large fields and minimum dose of 5040 rad in 28 fractions within a boost field). Results were compared with a group of 103 previously analyzed patients treated with surgery alone at MGH. A statistically significant decrease in local recurrence was seen in four of the six irradiated subgroups (modified Astler-Coller Stages B2g, B3, C1 + C2m, and C2g) at an interval 3 years from resection. This improvement was achieved with no increase in small bowel complications (4% with XRT versus 5% with surgery alone) in view of efforts at surgical reconstruction and use of multiple-field XRT techniques, bladder distension, etc.