Equivalent racial outcome after conformal radiotherapy for prostate cancer: a single departmental experience.

PURPOSE: African-American (AA) men with prostate cancer present with advanced disease, relative to white (W) men. This report summarizes our clinical and biochemical control (bNED) rates after conformal radiotherapy (RT). In particular, we aim to characterize any race-based outcome differences seen after comparable treatment. PATIENTS AND METHODS: We reviewed 893 patients (418 AA and 475 W) with clinically localized prostate cancer treated between 1988 and 1997. Neoadjuvant hormonal blockade was used in 22.5% of cases, and all patients received conformal RT to a median dose of 68 Gy (range, 60 to 74.8 Gy). Biochemical failure was defined according to the American Society of Therapeutic Radiology and Oncology consensus definition. Median follow-up was 24 months (range, 1 to 114 months). RESULTS: The 5-year actuarial survival, disease-free survival, and bNED rates for the entire population were 80.5%, 70.0%, and 57.6%, respectively. When classified by prognostic risk category, the 5-year actuarial bNED rates were 78.7% for favorable, 57.7% for intermediate, and 39.8% for unfavorable category patients. AA men presented at younger ages and with more advanced disease. Controlled for prognostic risk category, AA and W men had similar 5-year actuarial bNED rates in favorable (78% v 79%, P: = .91), intermediate (52% v 62%, P: =.44), and unfavorable categories (36% v 45%, P: = .09). Race was not an independent prognostic factor (P: = .36). CONCLUSION: Conformal RT is equally effective for AA and W patients. More research is needed in order to understand and correct the advanced presentations in AA men. These data suggest a need for early screening in AA populations.

Methotrexate, vinblastine, doxorubicin and cisplatin followed by radiotherapy or surgery for muscle invasive bladder cancer: the University of Chicago experience.

A total of 29 patients with muscle invasive bladder cancer, clinical stage T2N0 (12), T3aN0 (9), T3bN0 (5), T3N2 (2) or T4N2 (1), underwent 2 to 4 cycles of neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) chemotherapy followed by either radiotherapy (15), radical cystectomy (11) or no local therapy (3). The overall response rate to M-VAC chemotherapy was 69%, with 31% clinical complete responses and 38% clinical partial responses. A functioning bladder was maintained in 55% of the responding patients, although bladder wall calcifications were observed in 4 of 15 irradiated patients. Overall survival was 71% and disease-free survival was 55% at a median followup of 57 months. For the 12 stage T2N0 cancer patients overall survival was 100% at a median followup of 52 months. For the stages T3a and T3bN0 cancer patients overall survival was 63%, while all 3 node positive patients died. Neoadjuvant chemotherapy with a modified M-VAC regimen is well tolerated and may result in bladder preservation.

Racial differences in prostate-specific antigen levels in patients with local-regional prostate cancer.

Prostate cancer is a significant health problem for blacks. The incidence and mortality rates are higher in blacks than in whites; blacks often present with a higher stage. Prostate-specific antigen (PSA) is a very useful serum marker in prostate cancer. We analyzed data from a cohort of 161 patients to determine whether there were any racial differences in PSA levels prior to treatment in local-regional prostate cancer. The immunoradiometric method was used to determine the PSA values. The mean PSA levels were significantly higher in blacks than in whites (P = 0.022), and the difference remained significant in multivariate analysis after adjusting for stage and grade (P = 0.020). However, when analyzed further, the difference was statistically significant in one hospital (P = 0.001) and not in another (P = 0.493). Thus, our results are not unequivocal, but our data do suggest that racial differences in PSA levels not accounted for by tumor stage or grade may exist. Assuming that the data truly reflect a racial difference, the cause(s) of this difference remains to be determined. It may exist because, within each clinical stage, blacks are presenting with a higher tumor cell burden, or it may be indicative of more aggressive biological behavior. The possibility that racial differences are due to socioeconomic factors was considered by estimating median income level from zip code of residence; although a correlation between socioeconomic status and PSA level was found, racial differences remained borderline significant (P = 0.055) after adjusting for income level (in addition to stage and grade).

Recent advances in radiation therapy for head and neck cancer.

The most efficacious treatment method for head and neck cancer is not yet defined. However, there have been some improvements made in the radiotherapy of head and neck cancer that are encouraging. Both hyperfractionated radiation therapy and accelerated radiation therapy have improved the local control rates in numerous primary sites, and the results of more rigorous prospective randomized studies, if positive, will justify more routine use of these techniques. The use of neutrons for unresectable salivary gland tumors has clearly been established as the treatment of choice. Local control as well as cosmetic outcome is excellent, with the only disadvantage being that neutron therapy is not as widely used as photon radiation. The same is true for charged particle therapy, the greatest utility of which appears to be for relatively small tumors adjacent to critical structures such as the brain and spinal cord. We also believe that intraoperative radiation therapy shows great promise and may soon be more widely available for the treatment of head and neck cancers. However, we believe that the most exciting advancement in the treatment of head and neck cancer is the use of concomitant radiation therapy and chemotherapy, a topic that is discussed in detail in another article in this issue.

Radiotherapy with concomitant chemotherapy for head and neck cancer.

Concomitant chemoradiotherapy has already resulted in statistically significantly improved disease-free and overall survival for patients with head and neck cancer. Although the differences observed so far have been small, it is of note that the improved outcome was achieved even though only single-agent chemotherapy was used. More recent, chemoradiotherapy schedules have employed more aggressive chemotherapy regimens, frequently with split-course radiotherapy. Several of these schedules have resulted in encouraging response and survival figures in phase II trials. At the same time, toxicities, usually in the form of mucositis, have also been increased. The role of these schedules in the management of patients with advanced head and neck cancer will need further evaluation, eventually using a randomized format comparing such a regimen with standard radiotherapy alone. Their use outside of clinical trials cannot be recommended yet.

Curative radiotherapy following chemotherapy for invasive bladder carcinoma (a preliminary report).

Twenty-five patients with invasive transitional cell carcinoma of the bladder (Stage T2, T3, T4) received combined modality therapy using four cycles of methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) chemotherapy followed by surgery or radiation therapy (RT). Sixteen patients had complete (N = 8) or partial (N = 8) response to MVAC. Curative RT was delivered to 11 responders with T2 or T3 disease and to 2 patients with T4 disease. All 11 with T2 and T3 disease are currently alive, 7 with normal bladder function. The two with T4 disease are dead of disease. Three patients required salvage cystectomy for local recurrence and one patient had cystectomy for bladder stones. Follow-up ranged from 11 to 50 months with a median of 31 months. No late chemo-radiotherapy treatment-related complications to the intestines or in bladder function (other than one bladder stone formation) occurred. These preliminary results are encouraging and warrant further evaluation of this innovative approach in treating invasive carcinoma of the bladder. T2 and T3 patients with a complete or partial response to MVAC may be excellent candidates for a bladder-sparing treatment.

Palliative radiotherapy.

We have reviewed the role of radiation therapy in the palliative treatment of patients with non-small cell lung cancer. The use of radiation treatment results in effective palliation of chest symptoms such as dyspnea, cough, hemoptysis, and chest pain. In addition, the pain and suffering associated with skeletal and hepatic metastases are effectively alleviated by radiation therapy with minimal morbidity. Devastating neurologic complications can be avoided or alleviated in a great proportion of patients undergoing radiation therapy for cerebral metastases and spinal cord compression. Therefore, radiation therapy is a potent modality in relieving or reducing the suffering of patients with lung cancer. This is also a modality that has wide applicability; very few patients are not suitable candidates for that has wide applicability; very few patients are not suitable candidates for treatment regardless of their performance status. The aim of the treatments should always be prompt intervention using radiation therapy schedules that will minimize treatment time yet produce the desired results in a high proportion of patients. Protracted radiation schedules are not warranted in such patients except in special clinical situations. Palliation with radiation therapy is achieved quite promptly, with minimal side effects and a very small risk of any long-term consequences in patients who have a limited life expectancy.

Radiobiological characterization of head and neck and sarcoma cells derived from patients prior to radiotherapy.

The radiobiological parameters of 33 tumor cell lines were studied in biopsy samples obtained from patients prior to radiotherapy. Epithelial tumor cells derived from head and neck cancer patients were more radioresistant than tumor cell lines derived from patients with sarcoma regardless of method of analysis. The presence of radioresistant tumor cell lines was associated with local failure in some patients. However, the presence of radiosensitive tumor cells did not necessarily predict local control. Our data suggest radiocurability is complex and inherent radiobiological parameters of tumor cells may be only one factor in radiotherapy outcome.

Breast conserving surgery and definitive irradiation for early stage breast cancer.

Breast conserving surgery and postoperative breast radiotherapy were used to treat 219 cases of AJCC Stage I and II breast carcinoma at the Michael Reese and University of Chicago Hospitals. Most patients were treated with lumpectomy and axillary sampling followed by breast irradiation to a dose of 46 Gy followed by a boost dose of 14-16 Gy to the surgical bed. The 5-year actuarial local control is 92%. Follow-up is 1 to 10 years and the median follow-up is 36 months. Of the seven patients who recurred in the breast, three failed in the boost site and three failed adjacent to the boost site. The seventh patient recurred diffusely in the breast and skin. Four of the seven recurrences were in patients with positive surgical margins. The 5-year actuarial relapse-free survival is 80%. Factors which had an adverse affect on the cosmetic results were a scar length greater than 8 cm and a volume of resected breast tissue greater than 100 cm3. Treatment related complications were minor and infrequent. Breast conserving surgery followed by radiation therapy is effective in achieving local control with good to excellent cosmetic results.

Hydroxyurea, fluorouracil, and concomitant radiotherapy in poor-prognosis head and neck cancer: a phase I-II study.

Hydroxyurea and fluorouracil (5-FU) are active cytotoxic drugs in head and neck cancer and have shown synergistic activity in vitro. Both drugs also act as radiosensitizers. Therefore, we administered radiotherapy at daily fractions of 180 to 200 cGy with simultaneous continuous infusion 5-FU at 800 mg/m2/d and escalating daily doses of hydroxyurea for five days. Cycles were repeated every other week until completion of radiotherapy. Thirty-nine inoperable patients were treated at six dose levels of hydroxyurea ranging from 500 mg to 3,000 mg orally daily. Little effect of hydroxyurea on the WBC or platelet count was noted in patients receiving less than 2,000 mg daily, whereas both parameters decreased progressively in patients receiving 2,000 mg daily or more. Mucositis occurred at all dose levels, requiring frequent dose reduction of 5-FU; however, in patients receiving a daily hydroxyurea dose of 2,000 mg or less, the median weekly 5-FU dose administered was 1,725 mg/m2 (86% of the intended 5-FU dose), whereas at daily hydroxyurea doses exceeding 2,000 mg, the median weekly 5-FU dose decreased to 1,133 mg/m2 (57%) (P = .001). Of 15 evaluable patients with recurrent disease after prior local therapy only one failed to respond; six had a complete response (CR), and eight a partial response (PR). Of 17 evaluable patients without prior local therapy, 12 had a CR, with no patient developing recurrence in the irradiated field to date; five patients had a PR. We conclude that the recommended dose of hydroxyurea in this regimen is 2,000 mg daily. That dose will cause mild to moderate myelosuppression and will allow for delivery of greater than 80% of the intended 5-FU dose. The activity of this regimen in poor-prognosis head and neck cancer exceeds 90%; its further investigation in previously untreated patients is warranted.

Concomitant hydroxyurea, 5-fluorouracil, and radiation therapy for recurrent head and neck cancer: early results.

We tested the combination of hydroxyurea (HU), 5-fluorouracil (5-FU), and concomitant radiotherapy (XRT) in a group of patients with advanced or recurrent head and neck cancer. Both drugs are effective single agents, have shown synergistic activity in vitro, and can act as radiation sensitizers. A 5-day course of radiotherapy, with simultaneous HU and continuous infusion 5-FU, was followed by a 9-day rest period; cycles were repeated until completion of XRT. Sixteen patients have completed their therapy. Eleven patients had recurrent disease after previous therapy with surgery (11 patients), radiotherapy (9 patients), and combination chemotherapy (4 patients). Five patients had not received previous local therapy. These patients had persistent disease after induction chemotherapy and/or were inoperable because of poor general medical condition. Of 15 patients evaluable for response, 9 had complete response, including 5 patients who had earlier local therapy; 5 had partial response; and 1 failed to respond. Toxicities included mild myelosuppression and mucositis. No unusual complication related to previous radiotherapy was observed. This regimen has shown impressive activity in a cohort of patients who are not usually responsive to other types of currently available therapy. We are continuing our investigation to further define efficacy, toxicity, and maximally tolerated doses of this regimen.

Sequential administration of methotrexate, cisplatin, and 5-fluorouracil in multimodal therapy for locally advanced head and neck cancer.

Thirty-eight previously untreated patients with locally advanced head and neck cancer received three cycles of induction chemotherapy with methotrexate (120 mg/m2) followed by cisplatin (100 mg/m2) and a 5-day continuous infusion of 5-fluorouracil (1,000 mg/m2 per day). The response rate in 34 evaluable patients was 94%, with a complete response rate of 26%. Thirty-one patients underwent local therapy following induction chemotherapy, and 25 (81%) were rendered free of disease: 14 of 15 treated with surgery and radiotherapy and 11 of 16 treated with radiotherapy alone. At a median follow-up of 11 months, 8 patients have relapsed while the remaining 17 patients continue free of disease. The dose-limiting toxicity of chemotherapy was mucositis resulting in reduction of the 5-fluorouracil dose in 28 patients. This regimen is highly effective in inducing responses in patients with locally advanced head and neck cancer; 81% of the patients who complete local therapy are rendered free of disease with this multimodal approach. Due to short follow-up, the relapse rate, overall survival, and disease-free survival cannot yet be determined.

[A case of internal ophthalmomyiasis in Kenya (author's transl)]. / Ein Fall von Ophthalmomyiasis interna in Kenia.

An unusual case of ophthalmomyiasis is reported, in which two living fly larvae were observed inside the patient's eye. One larva was removed from the anterior chamber by paracentesis; the other was destroyed on the retina by photocoagulation. The mode of infestation, clinical picture and treatment are discussed in brief.

Acute haemorrhagic conjunctivitis and enterovirus 70 in Kenya.

The pandemic of acute haemorrhagic conjunctivitis that started in Ghana in 1969 and spread to many countries in Africa, Asia and Europe reached Kenya in April 1971. From one patient virus was isolated. This was possibly the first strain ever isolated of Enterovirus 70. Identification took time and was finished long after the publication of isolation of the new virus in Japan. Cross neutralization tests with the virus from Japan showed close relationship between the two. During a second epidemic in Kenya in 1974 many more strains of the virus were isolated. The history of isolation and identification and the clinical picture of the disease as seen in Kenya are described.