Harmar D. Brereton

Ten-Year Follow-Up of Radiation Therapy Oncology Group Protocol 92-02: A Phase III Trial of the Duration of Elective Androgen Deprivation in Locally Advanced Prostate Cancer

PURPOSE To determine whether adding 2 years of androgen-deprivation therapy (ADT) improved outcome for patients electively treated with ADT before and during radiation therapy (RT). PATIENTS AND METHODS Prostate cancer patients with T2c-T4 prostate cancer with no extra pelvic lymph node involvement and prostate-specific antigen (PSA) less than 150 ng/mL were included. All patients received 4 months of goserelin and flutamide before and during RT. They were randomized to no further ADT (short-term ADT [STAD] + RT) or 24 months of goserelin (long-term ADT [LTAD] + RT). A total of 1,554 patients were entered. RT was 45 Gy to the pelvic nodes and 65 to 70 Gy to the prostate. Median follow-up of all survival patients is 11.31 and 11.27 years for the two arms. RESULTS At 10 years, the LTAD + RT group showed significant improvement over the STAD + RT group for all end points except overall survival: disease-free survival (13.2% v 22.5%; P < .0001), disease-specific survival (83.9% v 88.7%; P = .0042), local progression (22.2% v 12.3%; P < .0001), distant metastasis (22.8% v 14.8%; P < .0001), biochemical failure (68.1% v 51.9%; P <or= .0001), and overall survival (51.6% v 53.9%, P = .36). One subgroup analyzed consisted of all cancers with a Gleason score of 8 to 10 cancers. An overall survival difference was observed (31.9% v 45.1%; P = .0061), as well as in all other end points herein. CONCLUSION LTAD as delivered in this study for the treatment of locally advanced prostate cancer is superior to STAD for all end points except survival. A survival advantage for LTAD + RT in the treatment of locally advanced tumors with a Gleason score of 8 to 10 suggests that this should be the standard of treatment for these high-risk patients.

A prospective study of treatment techniques to minimize the volume of pelvic small bowel with reduction of acute and late effects associated with pelvic irradiation

The volume, distribution, and mobility of opacified pelvic small bowel (PSB) were determined by fluoroscopy and orthogonal radiographs in 150 consecutive patients undergoing pelvic irradiation. Various techniques including uteropexy, omental transposition, bladder distention, inclining the patient, and anterior abdominal wall compression in the supine and prone treatment position were studied for their effect on the volume and location of small bowel within the pelvis. Abdominal wall compression in the prone position combined with bladder distention was selected for further investigation because of its simplicity, reproducibility, patient comfort, and ability to displace the small bowel. Factors correlating with the volume of pelvic small bowel (PSB) included prior pelvic surgery, pelvic irradiation (XRT), and body mass index. After pelvic surgery, especially following abdominoperineal resection (APR), there was a greater volume of PSB which was also less mobile. The severity of acute gastrointestinal effects positively correlated with the volume of irradiated small bowel. Overall, 67% of patients experienced little or no diarrhea, 30% developed mild diarrhea, and no patient required treatment interruption. Late gastrointestinal effects correlated with the prior pelvic surgery and with the volume of small bowel receiving greater than 45 Gy. Small bowel obstruction was not observed in 75 patients who had no previous pelvic surgery. However, following pelvic surgery excluding APR, 2/50 patients and following APR, 3/25 patients developed small bowel obstruction.

Predicting the course of Gompertzian growth

THE increase in volume or size with time that characterises many biological and physical systems is often well approximated retrospectively by mathematical ‘growth curves’. In some cases, however, growth may be sufficiently complicated for it to be impossible to predict later portions of the growth curve if observations are limited to a few early points. We report here the development of a generalised approach to the analysis of “Gompertzian” growth which enables accurate predictions of future growth for two model tumour systems. This mathematical method may be useful clinically, and expresses a property of biological growth that may be applicable to other systems.

Adriamycin and Enhanced Radiation Reaction in Normal Esophagus and Skin

Clinical evaluation of 10 patients with small cell carcinoma of the lung treated with radiotherapy and periodic cycles of combination chemotherapy with cyclophosphamide, vincristine, and adriamycin showed frequent and occasionally severe esophageal and skin reactions. Eight of the 10 patients had esophagitis, four required supportive intravenous fluids, and two subsequently developed esophageal narrowing and stricture formation. Recurrent esophagitis with augmentation of injury in the recently irradiated esophagus was observed 11 times in eight of the 10 patients after cycles of chemotherapy, and contributed to the sustained toxicity seen in two patients. Dermatitis in the form of moist desquamation was observed in five of the patients at very low doses of supervoltage radiation therapy. Acute pulmonary reactions was notably absent. This combination of chemotherapy, particularly adriamycin, potentiates the effect of radiotherapy on the normal esophagus and skin, and further implicates the radiosensitizing property of adriamycin.

Follow-up neurological evaluation in patients with small cell lung carcinoma treated with prophylactic cranial irradiation and chemotherapy

Abstract The safety of prophylactic cranial irradiation (PCI) has recently been questioned, based on reports of computerized tomographic abnormalities mainly seen in children, who received PCI and chemotherapy, primarily for acute lympbocytic leukemia. In order to clarify the significance of these findings, we examined a series of adult patients who were long term survivors (18–48 months, median 26 months, after all treatment). These patients were treated with combination radiotherapy and chemotherapy for small cell lung carcinoma and received cranial irradiation in the absence of known brain involvement by tumor. Patients were divided into three groups: three patients who received PCI + intrathecal metbotrexate (MTX) (Group 1), and ten who received only PCI (Group 2). An additional three patients (Group 3) were identified as long term survivors (41–70 months after all treatments) of a similar treatment program without any central nervous system (CNS) prophylaxis. All patients received an extensive evaluation of a variety of clinical parameters, EEG, and computer tomography (CT). Although CT abnormalities were detectable (mild cerebral atrophy in eight patients, encephaiomalacia in one of the 13 patients with CNS prophylaxis, and wild atrophy in two of the three patients without CNS prophylaxis~ so significant clinical abnormalities or EEG changes were detectable. While this group of patients is small, it is a unique cohort: adults who have received cranial irradiation in the absence of known brain tumor with long term follow-up. The precise role of CNS prophylaxis in the etiology of CT abnormalities is unclear, and the lack of clinically significant changes would suggest no contraindication to PCI when indicated.

Mixed anaplastic small-cell and squamous-cell carcinoma of the lung.

Excerpt The pleomorphism of lung cancer is well known and the appearance of histologically well and poorly differentiated areas within a tissue specimen, or even the coexistence of multiple discree...

Acute non‐lymphocytic leukemia and acute myeloproliferative syndrome following radiation therapy for non‐hodgkin's lymphoma and chronic lymphocytic leukemia. Cytogenetic studies

Seven cases of acute nonlymphocytic leukemia (ANLL) and one of malignant myeloproliferative syndrome were identified from a pool of 189 cases of non‐Hodgkins lymphoma (NHL) and CLL treated primarily with extensive radiotherapy at the Clinical Center, the National Institutes of Health. Four patients also received chemotherapy, two for only short periods. The median time interval from the diagnosis of the primary malignancy to the development of leukemia was 61 months (range 33 to 98 months) and the median survival after the diagnosis of leukemia was two months (0 to 9 months). All eight patients were cytogenetically abnormal and serial chromosome studies revealed that hypodiploidy was the most commonly observed chromosomal abnormality. Abnormalities of chromosome #7 were seen in all five patients analyzed by the chromosome banding technique; four of them had monosomy 7. The next most frequently involved chromosome was #5. The complexity, extensive nature, and long duration of the cytogenetic abnormalities prior to the diagnosis of leukemia in these patients may be characteristic of secondary leukemia in radiation‐treated lymphoma and the presence of such anomalies may predict leukemic transformation.

Adriamycin and Radiation: Synergistic Cardiotoxicity

Excerpt To the editor: Severe cardiomyopathy with irreversible congestive heart failure from adriamycin is very rare if the dose is limited to below 500 to 550 mg/m2body surface area (1, 2). We hav...

“Total” Therapy for Small Cell Carcinoma of the Lung

Seventy-one consecutive patients with small cell carcinoma of the lung were treated with an integrated approach between November, 1974, and May, 1977. The regimen included radiotherapy to the primary site, relatively brief (6 to 12 weeks) although intensive chemotherapy, and prophylactic cranial irradiation. Complete responses were achieved in 75% and 40% of patients with limited and extensive disease, respectively. Modest prolongation of survival (median, 10 months) was realized by patients with extensive disease, but prolonged relapse-free survival was not observed. In contrast, one-half of the patients with limited disease who achieved a complete response have remained clinically free of disease without further treatment for a mean of 18 months (range, 6 to 33 months). Since all relapses to date have been noted within the first year following cessation of treatment, this experience suggests there may be a potential for cure in those survivors who are now relapse free for intervals exceeding two years.

Hodgkin's disease and granulomatous angiitis of the central nervous system

Granulomatous angiitis of the central nervous system, a pathologic entity associated previously with a fatal prognosis, is reported in a patient with Hodgkins disease. Viral isolation, indirect fluorescent antibody, and electron microscopic studies performed on fresh cerebral tissue were negative. The granulomatous angiitis of the central nervous system in this patient remitted following therapy for Hodgkins disease. The epidemiologic, clinical and pathologic data in all reported cases of granulomatous angiitis of the central nervous system suggest that it: 1) may have more than one etiology; 2) may not always be fatal; 3) is associated with varicella‐zoster virus and Hodgkins disease; 4) is one of two granulomatous reactions found in association with Hodgkins disease; and when found with Hodgkins disease, 5) may remit with adequate therapy for the lymphoma.