Radical resection of periampullary tumors in the elderly: evaluation of long-term results.

Increasingly, patients of advanced age are coming for evaluation of periampullary tumors. Although several studies have demonstrated the safety of resecting periampullary tumors in older patients, few long-term survival data have been reported. Between 1983 and 1992 various periampullary masses were resected in 70 patients over age 65 (range 65-87 years). Total pancreatectomy was performed in 11 patients, and 59 patients underwent pancreaticoduodenectomy. The mean duration of hospitalization was 17 +/- 15 days. Major complications occurred in 27 patients (39%), and operative mortality rate was 8.5%. Overall median survival was 24 months; and 5-year survival was 25%. Perioperative outcome was compared in patients aged 65 to 74 years and in patients > or =75 years old. The older age group required longer periods in the surgical intensive care unit postoperatively, but the long-term survival was similar in the two age groups. Radical resection with the intent to cure periampullary tumors is safe in selected patients of advanced age, and long-term survival is in the range of expected survival for younger patients with the same tumors.

Does a radiation dose-response relation exist concerning survival of patients who have soft-tissue sarcomas of the extremities? Radiation dose-response relation for soft-tissue sarcomas.

This study analyzes a single-institution experience by evaluating the impact on survival of increasing total dose of adjunctive irradiation in patients who had extremity soft-tissue sarcoma (ESTS). A retrospective review of the tumor registry at a university medical center from January 1984 through December 1992 yielded a total of 59 surgical patients of ESTS. With follow-up ranging from 30 to 135 months (median, 65 months), the 2-, 5-, and 8-year overall and disease-free survival for all patients was 86%, 71%, 58% and 76%, 70%, 56%, respectively. Multivariate analyses using the Cox proportional hazards model revealed that total radiation dose (p = 0.02), American Joint Committee on Cancer stage (p = 0.04), and tumor size (p = 0.006) were all significant prognostic factors of overall survival; however, only tumor size was predictive of disease-free survival (p = 0.02). When the effect of tumor size and disease stage were controlled in the Cox model, a dose-response curve between increasing total radiation dose and improved overall patient survival was indicated. This study demonstrates the significance of tumor size on predicting both overall and disease-free survival in patients who have soft-tissue sarcomas of the extremity. It also suggests, however, that a radiation dose-response relation may exist for overall survival. Future investigations should consider evaluating the minimal total radiation dose needed to optimize patient survival after limb-sparing surgery.

A Phase II trial of neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin in the treatment of patients with locally advanced breast carcinoma.

BACKGROUND: Traditionally, primary surgical therapy is considered unsuitable for the treatment of patients with locally advanced breast carcinoma (LABC). Multiple reports have documented the efficacy of primary chemotherapy in this group of patients. The purpose of this study was to investigate the efficacy of a multimodality treatment program in reducing distant and local disease relapses in patients with LABC. METHODS: Fifty-five patients with large operable or inoperable Stage III breast carcinoma, median tumor greatest dimension 7 x 8 cm, were treated with neoadjuvant MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) to achieve maximum clinical response, followed by modified radical mastectomy, adjuvant MVAC for six courses, and chest wall radiation. Of these patients, 37 had Stage IIIA disease and 18 had Stage IIIB or inflammatory breast carcinoma. RESULTS: Forty-nine patients achieved overall responses to the neoadjuvant chemotherapy, including 16 complete clinical remissions. Histopathologic evaluation was performed for all patients; nine were pathologically free of disease and six had residual intraductal carcinoma only. After a median follow-up of 47 months (range, 8-76 months), 24 patients had relapsed: 6 locoregional and distant, and 18 distant only. The median disease free and overall survival have not been reached; the 5-year disease free and overall survival rates are 51% and 63%, respectively. The number of lymph nodes with metastases was found to be an independent predictor of relapse in univariate and multivariate analyses. CONCLUSIONS: This multidisciplinary approach produced an excellent local control rate and a respectable 5-year distant relapse free rate. Axillary lymphadenectomy after primary chemotherapy provides crucial prognostic information, which can be important in planning multimodality treatment of patients with LABC.

Adenocarcinoma of the fallopian tube: results of a multi-institutional retrospective analysis of 72 patients.

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 < or = 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 FIGO 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 II and higher.

Natural history and prognostic factors for survival in patients with acquired immune deficiency syndrome (AIDS)-related primary central nervous system lymphoma (PCNSL).

The incidence of primary central nervous system lymphoma (PCNSL) is increasing rapidly. It will be the most common primary malignant neoplasm of the brain by the year 2000. PCNSL is an important lethal complication in acquired immunodeficiency syndrome (AIDS) patients. Our objective was to study the natural history and prognostic factors for survival in patients with AIDS-related PCNSL. This is a retrospective cohort study of 75 patients with the diagnosis of AIDS-related PCNSL followed at Jackson Memorial Hospital/University of Miami. Medical records were abstracted for information about age, gender, race, and ethnicity. The method of diagnosis, treatment, and outcome of AIDS and PCNSL in this group were examined. Univariate and multivariate analyses were performed to identify prognostic factors for survival. The median age was 37 years. Males comprised 84% of the patients and 55% of the patients were Hispanic. The most common human immunodeficiency virus (HIV) risk factors were homosexuality and multiple sexual partners. The median cluster designation (CD) 4 count was 15/microl and the median lactic dehydrogensase (LDH) was 1.5x normal. Computed-assisted tomographic (CT) scans of the brain showed multiple lesions in 44% of the patients. Single-photon emission CT scan (SPECT) Thallium-201 of the brain was performed in two-thirds of patients. The most common histologies were immunoblastic and large cell lymphoma. Cranial radiation was given to 72% of the patients, and 55% of them did not complete treatment. The median survival of the group was 1.3 months. Univariate and multivariate analysis showed that longer survival was associated with good performance status (ECOG = 1 to 2 vs. 3 to 4). The presence of prior opportunistic infections, risk factors for AIDS, CD4 counts, level of LDH, ethnicity, gender, duration of symptoms before diagnosis, and race did not influence survival. PCNSL is a neoplasm with a very poor prognosis and short survival even with CNS radiation therapy. Performance status appears to be the main prognostic factor for survival. No significant differences in presentation or outcome were detected between the Hispanic and non-Hispanic patients.

Management of stage I-B, II-A, and II-B carcinoma of the cervix with high-dose-rate brachytherapy: initial results of an institutional clinical trial.

In 1989, the University of Miami began a program incorporating high-dose-rate (HDR) brachytherapy into the definitive treatment of patients with invasive carcinoma of the cervix. Patients received an average total dose to point A of 5,511 cGy (range 4,280-6,360 cGy) in an average of 57 days (range 39-84 days). An analysis of the first 24 cases found 11 FIGO Stage I-B, four Stage II-A, and nine Stage II-B tumors. At the end of all radiation therapy, 19/24 patients' tumors (79.2%) had undergone a clinical complete response (CR). With median follow-up of 26 months (range 14-63 months), three have relapsed locally, two regionally, and six in extrapelvic sites. Almost two-thirds of all failures occurred in patients with tumors >4 cm, who also took more than 8 weeks to complete their treatment. Overall 2-year actuarial survival for the entire study group is approximately 74%. A univariate analysis determined that clinical stage (P = 0.02), overall treatment time (P = 0.03), tumor size (P = 0.05), and response at the end of therapy (P = 0.005) were significant prognostic factors. Multivariate analysis showed that tumor response to therapy was the most important prognosticator of outcome (P = 0.001). Besides five cases of apical vaginal stenosis, there have been no reported chronic complications in this cohort of patients. A prospectively randomized trial is recommended to compare the efficacy of HDR vs. low-dose-rate brachytherapy in cervical carcinoma.

Retrospective epidemiologic analysis of patients diagnosed with intracranial meningioma from 1977 to 1990 at the Jackson Memorial Hospital, Sylvester Comprehensive Cancer Center: the Jackson Memorial Hospital Tumor Registry experience.

A descriptive analysis was performed of the Tumor Registry data for intracranial meningioma by the Jackson Memorial Hospital, University of Miami School of Medicine Tumor Registry. A total of 108 cases of intracranial meningioma was collected and reviewed. Overall survival for 2, 5, and 10 years was 82, 72, and 60%, respectively. There was no difference in survival for males and females at 5 years, nor any difference in survival for race or ethnicity. There was a trend for improved survival for the young age group (18-55 years).

Quality of life: radical prostatectomy versus radiation therapy for prostate cancer.

PURPOSE: The impact of radical prostatectomy and external beam radiotherapy on the quality of life of patients was compared. MATERIALS AND METHODS: A total of 136 patients underwent radical prostatectomy and 60 underwent external beam radiotherapy for clinically localized prostate cancer. Patients were asked to complete a questionnaire containing The Functional Living Index: Cancer, the Profile of Moods States, and a series of questions evaluating bladder, bowel and sexual function. RESULTS: The radical prostatectomy group had worse sexual function and urinary incontinence, while the external beam radiotherapy group had worse bowel function. Of the patients 90% from both groups stated that they would undergo the treatment again. CONCLUSIONS: Radical prostatectomy and external beam radiotherapy have comparable impact upon quality of life.

Phase II trial of recombinant interferon-alpha with BCNU, cisplatin, DTIC and tamoxifen in advanced malignant melanoma.

Since cytotoxic chemotherapy (BCNU, DTIC and cisplatin, tamoxifen) and interferon-alpha (IFN-alpha) have each produced responses in advanced malignant melanoma, a phase II trial was conducted to evaluate the response and toxicity of simultaneous administration of both therapies. Of 33 assessable patients, two (6%) had complete response (CR) and 12 patients (36%) had partial response (PR), for a total response rate (CR+PR) of 42% (95% confidence interval 26-58). Four patients had minor response (12%). Mixed responses occurred in five patients (15%). The remaining patients had progressive disease. The duration of CR was 3, 7 and 17 (+) months and the duration of PR was 3+ to 19+ months (median 6 months). The median overall survival for all patients entered into the study was 5 months. Main toxicities included myelosuppression and fatigue. Combined simultaneous cytotoxic chemotherapy and IFN produced a high response rate (42%) which is comparable to that reported for chemotherapy alone. Further studies are needed to determine the optimal schedule for combining chemotherapy and immunotherapeutic agents as well as the impact of biological agents on survival in the treatment of melanoma.

Lung cancer in patients with human immunodeficiency virus infection.

This retrospective study determined the clinical course of lung cancer in patients with human immunodeficiency virus (HIV) infection. A total of 23 patients with HIV infection archived as lung cancer were studied: 16 were identified from about 1,000 lung cancer patients entered in the tumor registry and medical records of Jackson Memorial Hospital, 7 were identified from about 1,000 HIV-positive patients entered in the Special Immunology registry of Veterans Administration Medical Center, 4 patients did not have pathologic confirmation of lung cancer, and 19 patients, all men, met the criteria for analysis (histopathologic diagnosis of lung cancer and HIV+ by serology). The median age was 47 (range: 36-66). Risk factors for HIV were homosexuality (6 patients), blood transfusion (3), promiscuity (5), intravenous drug abuse (4), and none (3). Six patients had a history of coexistent pulmonary tuberculosis and 5 had Pneumocystis carinii pneumonia. Median survival from diagnosis of lung cancer was 3 months. Advanced stages of both HIV infection and lung cancer may account for the poor survival. All patients were men and noted to be younger than other patients with lung cancer.

Prognostic significance of DNA aneuploidy in diffuse malignant mesothelioma.

DNA ploidy of pepsin digested preparations of 48 paraffin-embedded specimens from 19 patients with histologically confirmed malignant mesothelioma was determined by laser flow cytometry. Eight of the 19 tumors (42%) were diploid and 11 (58%) were aneuploid. Of the aneuploid tumors, only one showed multiploidy. The median survival time of the patients with diploid tumors was 19, 16, and 14 months from the onset of symptoms, diagnosis, and treatment, respectively. The median survival in patients with aneuploid tumors was 8, 7, and 7 months from the onset of first symptoms, diagnosis, and treatment. Thus, patients with diploid tumors lived longer than patients with aneuploid tumors. These results suggest that DNA ploidy analysis may be of prognostic value in malignant mesothelioma.

A randomized clinical trial in bronchogenic small-cell carcinoma evaluating alternating maintenance therapy of vincristine, adriamycin, procarbazine, and etoposide (VAPE) with cyclophosphamide, CCNU, and methotrexate (CCM) versus CCM maintenance alone in complete responders following VAPE induction and late intensification.

Initially, 109 evaluable patients with locally advanced or metastatic small cell lung cancer (SCLC) were treated with vincristine, Adriamycin, procarbazine, and etoposide (VAPE). Partial (PR) or nonresponders (NR) were crossed to CCM (cyclophosphamide, CCNU, and methotrexate) and then to HMiVe (hexamethylmelamine, mitomycin C, vinblastine) sequentially at maximum response. Complete responders (CR) were intensified by 50% with VAPE primarily and randomized to VAPE, alternating with CCM or CCM alone during maintenance. CR patients with limited disease received local thoracic irradiation and prophylactic cranial irradiation (PCI), whereas those with extensive disease received PCI alone. There were 45 patients (41%) who achieved a CR to chemotherapy, and 27 patients were eligible for randomization. Of 12 CR patients randomized to alternating therapy (VAPE/CCM), the median survival was 25.9 months compared to 12.9 months for 15 CR patients randomized to continuous CCM (P = .049). In addition, 35 patients achieved a PR (32%) and 29 were NR (27%). Overall median survivals were significantly different for the CR patients (13.0 months) as compared to PR (7.6 months) and NR patients (6.4 months). Late intensification did not appear to add substantially to survival while contributing to toxicity. In summary, VAPE is a new outpatient regimen for SCLC, which is highly effective as an induction regimen with moderate hematologic toxicity and predominantly gastrointestinal nonhematologic toxicity.

Melanoma in a southeastern Hispanic population.

A descriptive analysis was performed of the Tumor Registry data for malignant melanoma in Hispanics ascertained by the Jackson Memorial Hospital (JMH), University of Miami School of Medicine Tumor Registry. A total of 54 cases of melanoma in Hispanics was collected and reviewed. Most of the lesions of melanoma occurred on the trunk, arm, shoulder, leg, and hip. Seventy percent of the Hispanics presented with local stage disease; 26% presented with both regional and distant disease. Local stage had the best 5-year survival (87%). In regional and distant disease combined, the survival was better for Hispanics than non-Hispanics (p = 0.01). In addition, it was found that the Hispanics in the over 50-year-old age group did better than the non-Hispanics in the same group (p = 0.05). Comparison of survival between Hispanic males and females shows that Hispanic females have a 5-year survival of 86% compared to 56% for Hispanic males (p = 0.017).

Prognostic factors in lung cancer based on multivariate analysis.

Multivariate analysis was performed on 1,336 patients with lung cancer to determine the prognostic significance of stage, race, gender, age, and treatment in each histologic subtype. The study was designed to establish a subgroup of patients whose survival outcome might be better, based on these factors. On univariate analysis, stage and surgery were significant factors in each histologic subtype. The presence of liver metastases, was an important prognostic factor in all subtypes except large cell carcinoma. However, 131 of 140 patients with large cell carcinoma had liver metastases, and this factor may account for the observation that liver metastases was not a significant prognostic factor. In the multivariate analysis, good prognosis was associated with early stage disease and surgical treatment in all cell types. For a given stage, the improvements in relative risk due to surgery represent both the effect of treatment and the effects of other unmeasured patient characteristics, such as performance status and physiological status, that make the patient a suitable candidate for surgery.

The accuracy of the histological classification of lung carcinoma and its reproducibility: a study of 75 archival cases of adenosquamous carcinoma.

The classification of lung carcinoma into a small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC), is highly reproducible. There are few studies on the reproducibility of subtyping NSCLC, with anecdotal reports on the subtype of adenosquamous carcinoma. We undertook a study of 75 cases archived as adenosquamous carcinoma. All cases were accepted as NSCLC on independent review by three pathologists utilizing the 1982 World Health Organization (WHO) classification criteria. The acceptance rate of adenosquamous carcinoma by the three pathologists was 65%, 28%, and 65%. Cases not accepted as adenosquamous fell into the different subtypes of NSCLC, with a concordance rate between each pair of pathologists of 49%, 61% and 43%, indicating poor agreement between pathologists. The study confirms the high reproducibility of the classification into SCLC and NSCLC; it shows poor concordance for all subtypes of NSCLC with poor reproducibility of diagnosis of adenosquamous carcinoma as specified by the 1982 WHO classification. Physicians dealing with lung carcinoma should be aware of this limitation of classification.

New strategies are needed in diffuse malignant mesothelioma.

BACKGROUND: Medical records of 50 patients with malignant mesothelioma were reviewed to determine the clinical features and factors influencing survival. METHODS: Charts of all patients whose conditions were diagnosed as malignant mesothelioma were abstracted and analyzed by statistical software. RESULTS: The male-to-female ratio was 4:1. The age distribution was younger than 45 years of age, 10%; 45-54 years of age, 12%; 55-64 years of age, 37%; 65-74 years of age, 33%; and 75 years of age or older, 8%. Both mean and median ages were 58 years. Among the 32 patients in whom asbestos exposure was recorded, 24 had documented exposure. The sites were pleura, 73%; peritoneum, 20%; and both, 6%. The histologic types were epithelial, 51%; sarcomatous, 10%; mixed, 15%; and not specified, 24%. The stage at presentation was Stage I, 37%; II, 39%; III, 12%; IV, 6%; and unknown, 6%. The common symptoms in pleural disease were dyspnea and pain; in peritoneal disease, abdominal distension and pain were common. The median time from first symptom to diagnosis was 3 months (range, 0-23 months). The median survival after the appearance of symptoms, the diagnosis, and the treatment were 13, 10, and 8 months, respectively. CONCLUSIONS: The survival was independent of age, sex, and smoking behavior. It was longer in patients with earlier-stage disease, a good performance status, a longer duration of symptoms, an absence of pain, and who were treated with combined surgery and chemotherapy. Chemotherapy using anthracyclines yielded more remissions (9 of 21) than that using nonanthracyclines (0 of 13). The remission rate after primary chemotherapy with anthracyclines (7 of 16) may be higher than in recurrent tumor (2 of 14). In future trials, stratification into primary chemotherapy and chemotherapy of recurrent cancer is suggested. There is a need for multitechnique trials incorporating primary chemotherapy.

Lung cancer in patients with human immunodeficiency virus infection compared with historic control subjects.

Lung cancer infrequently may be associated with human immunodeficiency virus (HIV) infection. This retrospective case-control study was undertaken to determine if there were differences in age, sex, and stage distribution and in survival between HIV-positive and HIV-indeterminate lung cancer patients. We compared 19 patients with both pathologically verified lung cancer and HIV infection proved by serologic study with lung cancer patients with an indeterminate HIV status. All 19 HIV-positive lung cancer patients were men. This was significantly (p = 0.004) different from the 69 percent male preponderance in 1,335 HIV-indeterminate lung cancer patients. Median ages of HIV-positive and HIV-indeterminate patients were 48 and 61 years, respectively. HIV-positive patients were significantly (p = 0.0139) younger. Stage distribution was similar in both groups. Histologic features and smoking were not significantly different between the two groups. Survival data that were available in 16 HIV-positive patients were compared with 32 HIV-indeterminate control subjects matched for stage, age, sex, and race. The median survival was three months in the HIV-positive group and ten months in the HIV-indeterminate cohort. The survival was significantly different (p = 0.002). There were no one-year survivors in HIV-positive lung cancer patients.

The increasing recognition of adenosquamous lung carcinoma (1977-1986).

A retrospective analysis of the data in the tumor registry on all 103 patients with adenosquamous lung carcinoma diagnosed and treated at our center between 1977 and 1986 was performed. The history of tobacco use was available for 100 patients (72 men and 28 women). Ninety-four percent of the patients (100% of men and 79% of women) were smokers, suggesting that adenosquamous carcinoma may be a Kreyberg I type of lung carcinoma. The gender, race, and age distributions in adenosquamous carcinoma were similar to other histologic subtypes of lung carcinoma. Patients less than 45 years old constituted 10%; 45-54 years old, 24%; 55-64 years old, 34%; 65-74 years old, 25%; and greater than 75 years, 7%. In the 95 patients whose stage at the time of diagnosis was known, 11% had local stage; 28%, regional; and 61%, distant stage. The 1-, 2- and 5-year survival of the 103 patients were 27%, 18%, and 8%, respectively. Survival was related to stage. Local stage had the best survival, and greater than 50% of patients were alive at 4 years. Regional stage had an intermediate median survival of 10 months but no survivors at 5 years. Distant stage had the worst median survival (5 months), and one patient (2%) was alive at 3 years. There was a significant increase (two- to three-fold) in the frequency of adenosquamous carcinoma over the 10-year study period, 1977-1986.

Descriptive analysis of the tumor registry experience for malignant melanoma from 1977 to 1986 at the University of Miami School of Medicine/Jackson Memorial Hospital.

A descriptive analysis was performed of malignant melanoma data ascertained by the University of Miami School of Medicine/Jackson Memorial Hospital (UM/JMH) Tumor Registry. A total of 376 melanoma cases were collected and reviewed. Most of the melanoma lesions occurred on the trunk, especially in the 40- to 49- and 50- to 54-year-old age groups. Local-stage cases had the best 5-year survival--77%. The difference in survival between local-stage case and regional- and distant-stage cases was statistically significant (p = 0.0000). In males with local-stage disease, lesions on the trunk were associated with better survival than lesions at other sites (p = 0.04). In females with local-stage disease, survival was 68% for 5 years for trunk sites vs. 87% for other sites (p = 0.05). In local-stage disease, the overall 5-year survival was 85%.